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Short Arm (short + arm)
Selected AbstractsThe magnocellular theory of developmental dyslexiaDYSLEXIA, Issue 1 2001John Stein Abstract Low literacy is termed ,developmental dyslexia' when reading is significantly behind that expected from the intelligence quotient (IQ) in the presence of other symptoms,incoordination, left,right confusions, poor sequencing,that characterize it as a neurological syndrome. 5,10% of children, particularly boys, are found to be dyslexic. Reading requires the acquisition of good orthographic skills for recognising the visual form of words which allows one to access their meaning directly. It also requires the development of good phonological skills for sounding out unfamiliar words using knowledge of letter sound conversion rules. In the dyslexic brain, temporoparietal language areas on the two sides are symmetrical without the normal left-sided advantage. Also brain ,warts' (ectopias) are found, particularly clustered round the left temporoparietal language areas. The visual magnocellular system is responsible for timing visual events when reading. It therefore signals any visual motion that occurs if unintended movements lead to images moving off the fovea (,retinal slip'). These signals are then used to bring the eyes back on target. Thus, sensitivity to visual motion seems to help determine how well orthographic skill can develop in both good and bad readers. In dyslexics, the development of the visual magnocellular system is impaired: development of the magnocellular layers of the dyslexic lateral geniculate nucleus (LGN) is abnormal; their motion sensitivity is reduced; many dyslexics show unsteady binocular fixation; hence poor visual localization, particularly on the left side (left neglect). Dyslexics' binocular instability and visual perceptual instability, therefore, can cause the letters they are trying to read to appear to move around and cross over each other. Hence, blanking one eye (monocular occlusion) can improve reading. Thus, good magnocellular function is essential for high motion sensitivity and stable binocular fixation, hence proper development of orthographic skills. Many dyslexics also have auditory/phonological problems. Distinguishing letter sounds depends on picking up the changes in sound frequency and amplitude that characterize them. Thus, high frequency (FM) and amplitude modulation (AM) sensitivity helps the development of good phonological skill, and low sensitivity impedes the acquisition of these skills. Thus dyslexics' sensitivity to FM and AM is significantly lower than that of good readers and this explains their problems with phonology. The cerebellum is the head ganglion of magnocellular systems; it contributes to binocular fixation and to inner speech for sounding out words, and it is clearly defective in dyslexics. Thus, there is evidence that most reading problems have a fundamental sensorimotor cause. But why do magnocellular systems fail to develop properly? There is a clear genetic basis for impaired development of magnocells throughout the brain. The best understood linkage is to the region of the Major Histocompatibility Complex (MHC) Class 1 on the short arm of chromosome 6 which helps to control the production of antibodies. The development of magnocells may be impaired by autoantibodies affecting the developing brain. Magnocells also need high amounts of polyunsaturated fatty acids to preserve the membrane flexibility that permits the rapid conformational changes of channel proteins which underlie their transient sensitivity. But the genes that underlie magnocellular weakness would not be so common unless there were compensating advantages to dyslexia. In developmental dyslexics there may be heightened development of parvocellular systems that underlie their holistic, artistic, ,seeing the whole picture' and entrepreneurial talents. Copyright © 2001 John Wiley & Sons, Ltd. [source] An Xp; Yq Translocation Causing a Novel Contiguous Gene Syndrome in Brothers with Generalized Epilepsy, Ichthyosis, and Attention DeficitsEPILEPSIA, Issue 12 2003Michael J. Doherty Summary:,Purpose: We describe two brothers with generalized epilepsy, attention deficits, congenital ichthyosis, and Leri,Weill dyschondrosteosis who harbor an unusual Xp; Yq translocation chromosome, resulting in a novel contiguous gene syndrome because of deletion of genes from the distal short arm of the X chromosome. Methods: Physical examination, neuropsychologic testing, EEG, and neuroimaging studies were performed. Because of their unusual phenotype, karyotyping, fluorescence in situ hybridization, and further molecular analyses were carried out to refine the break points of the underlying unbalanced sex chromosome rearrangement. Results: The subjects had generalized epilepsy, X-linked ichthyosis, Madelung deformities, mesomelia, normal intelligence, and attention deficits. The brothers' karyotype was unbalanced; they inherited a maternal derivative X chromosome. Deleted distal Xp genes included short-stature homeobox on the X chromosome (SHOX), aryl sulfatase E (ARSE), variably charged X-chromosome mRNA gene A (VCX-A), and steroid sulfatase (STS). The final karyotype was 46,Y,der(X)t(X; Y)(p22.3; q11.2).ish der(X) (DXZ1+, KAL+, STS-, SHOX-) mat. Conclusions: Loss of distal contiguous Xp genes resulted in a syndrome comprising bony deformities, ichthyosis, attention problems, and generalized epilepsy. Candidate epilepsy genes within the deleted segment, such as ASMT, a gene involved in the final synthesis of melatonin, are discussed. Cytogenetic analyses should be included in the clinical evaluation of patients with generalized epilepsy and complex phenotypes. [source] Genes, chromosomes and the development of testicular germ cell tumors of adolescents and adultsGENES, CHROMOSOMES AND CANCER, Issue 7 2008Alan McIntyre Testicular germ cell tumors (TGCTs) of adults and adolescents are thought to be derived from primordial germ cells or gonocytes. TGCTs develop postpuberty from precursor lesions known as intratubular germ cell neoplasia undifferentiated. The tumors can be divided into two groups based on their histology and clinical behavior; seminomas resemble primordial germ cells or gonocytes and nonseminomas resemble embryonic or extraembryonic tissues at various stages of differentiation. The most undifferentiated form of nonseminoma, embryonal carcinoma, resembles embryonic stem cells in terms of morphology and expression profiling, both mRNAs and microRNAs. Evidence supports both environmental factors and genetic predisposition underlying the development of TGCTs. Various models of development have been proposed and are discussed. In TGCTs, gain of material from the short arm of chromosome 12 is invariable: genes from this region include the proto-oncogene KRAS, which has activating mutations in ,10% of tumors or is frequently overexpressed. A number of different approaches to increase the understanding of the development and progression of TGCTs have highlighted the involvement of KIT, RAS/RAF/MAPK, STAT, and PI3K/AKT signaling. We review the role of these signaling pathways in this process and the potential influence of environmental factors in the development of TGCTs. © 2008 Wiley-Liss, Inc. [source] Integration of amplified BCR/ABL fusion genes into the short arm of chromosome 17 as a novel mechanism of disease progression in chronic myeloid leukemiaGENES, CHROMOSOMES AND CANCER, Issue 1 2001Simone Metzke-Heidemann We describe the cases of two patients with Philadelphia chromosome,positive chronic myeloid leukemia (CML), in whom the extramedullary blastic phase developed during disease progression. The similar clinical presentations of these patients was accompanied by gain of identical secondary chromosome abnormalities, that is, monosomies 9, 14, and 22, and by a clustered amplification of the BCR/ABL fusion gene. The additional copies of the BCR/ABL fusion gene were integrated into the short arm of structurally abnormal chromosomes 17 in both patients. The conformity of these genetic features in two patients with a rare disease manifestation leads us to the assumption that either the clustered amplification of the BCR/ABL fusion gene or the integration of this cluster into the short arm of chromosome 17 or both are associated with extramedullar disease progression in CML. Furthermore, the insertion of amplified BCR/ABL fusion genes into structurally abnormal chromosomes provides a novel mechanism of disease progression in BCR/ABL -positive CML. © 2001 Wiley-Liss, Inc. [source] JKT-1 is not a human seminoma cell lineINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 4 2007Jeroen de Jong Summary The JKT-1 cell line has been used in multiple independent studies as a representative model of human testicular seminoma. However, no cell line for this specific tumour type has been independently confirmed previously; and therefore, the seminomatous origin of JKT-1 must be proven. The genetic constitution of the JKT-1 cells was determined using flow cytometry and spectral karyotyping, as well as array comparative genomic hybridization and fluorescent in situ hybridization. Marker profiling, predominantly based on differentially expressed proteins during normal germ cell development, was performed by immunohistochemistry and Western blot analyses. Moreover, genome wide affymetrix mRNA expression and profiling of 157 microRNAs was performed, and the status of genomic imprinting was determined. A germ cell origin of the JKT-1 cells was in line with genomic imprinting status and marker profile (including positive staining for several cancer-testis antigens). However, the supposed primary tumour, from which the cell line was derived, being indeed a classical seminoma, was molecularly proven not to be the origin of the cell line. The characteristic chromosomal anomalies of seminoma, e.g. gain of the short arm of chromosome 12, as well as the informative marker profile (positive staining for OCT3/4, NANOG, among others) were absent in the various JKT-1 cell lines investigated, irrespective of where the cells were cultured. All results indicate that the JKT-1 cell line is not representative of human seminoma. Although it can originate from an early germ cell, a non-germ cell derivation cannot be excluded. [source] A to G transitions at 260, 386 and 437 in DAZL gene are not associated with spermatogenic failure in Indian populationINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2006K. Thangaraj Summary The autosomal DAZL (Deleted-in- Azoospermic- Like) gene, mapped to the short arm of the human chromosome 3, is the precursor for the Y-chromosomal DAZ cluster, which encodes for putative RNA-binding proteins. Mutations in the DAZL have been reported to be associated with spermatogenic failure in Taiwanese population but not in Caucasians. As there was no study on Indian populations, we have analysed the entire coding sequences of exons 2 and 3 of DAZL in a total of 1010 men from Indian subcontinent, including 660 infertile men with 598 non-obstructive azoospermia, 62 severe oligozoospermia and 350 normozoospermic fertile control men, to investigate whether mutation(s) in the DAZL is associated with male infertility. Interestingly, none of our samples (1010) showed A386G (T54A) mutation, which was found to be associated with spermatogenic failure in Taiwanese population. In contrast, A260G (T12A) mutation was observed in both infertile and normozoospermic fertile control men, without any significant association with infertile groups (,2 = 0.342; p = 0.556). Similarly, we have found a novel A437G (I71V) mutation, which is also present in both infertile and normozoospermic fertile control men without any significant difference (,2 = 0.476; p = 0.490). Our study clearly demonstrates the complete absence of the A386G (T54A) mutation in Indian subcontinent and the other two mutations , A260G (T12A) and A437G (I71V) , observed are polymorpic. Therefore, we conclude that these mutations in the DAZL gene are not associated with male infertility in Indian subcontinent. [source] The von Hippel-Lindau tumor suppressor gene expression level has prognostic value in neuroblastomaINTERNATIONAL JOURNAL OF CANCER, Issue 3 2006Jasmien Hoebeeck Abstract Deletions of the short arm of chromosome 3 are often observed in a specific subset of aggressive neuroblastomas (NBs) with loss of distal 11q and without MYCN amplification. The critical deleted region encompasses the locus of the von Hippel-Lindau gene (VHL, 3p25). Constitutional loss of function mutations in the VHL gene are responsible for the VHL syndrome, a dominantly inherited familial cancer syndrome predisposing to a variety of neoplasms, including pheochromocytoma. Pheochromocytomas are, like NB, derived from neural crest cells, but, unlike NB, consist of more mature chromaffin cells instead of immature neuroblasts. Further arguments for a putative role of VHL in NB are its function as oxygen sensitizer and the reported relation between hypoxia and dedifferentiation of NB cells, leading to a more aggressive phenotype. To test the possible involvement of VHL in NB, we did mRNA expression analysis and sought evidence for VHL gene inactivation. Although no evidence for a classic tumor suppressor role for VHL in NB could be obtained, a strong correlation was observed between reduced levels of VHL mRNA and low patient survival probability (p = 0.013). Furthermore, VHL appears to have predictive power in NTRK1 (TRKA) positive tumor samples with presumed favorable prognosis, which makes it a potentially valuable marker for more accurate risk assessment in this subgroup of patients. The significance of the reduced VHL expression levels in relation to NB tumor biology remains unexplained, as functional analysis demonstrated no clear effect of the reduction in VHL mRNA expression on protein stability of its downstream target hypoxia-inducible factor ,. © 2006 Wiley-Liss, Inc. [source] Erythrokeratodermia variabilis (EKV) , eine Störung der epidermalen Expression von Gap-Junction-ProteinenJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 5 2005Erythrokeratodermia variabilis (EKV), a disorder due to altered epidermal expression of gap junction proteins Connexin,31; Connexin,43; Erythrokeratodermia variabilis; Gap Junctions Zusammenfassung Die Erythrokeratodermia variabilis (EKV) ist eine seltene autosomal-dominant vererbte Genodermatose mit einer epidermalen Verhornungsstörung. Das klinische Bild der EKV wird von zwei Morphen geprägt: transiente, schnell wandernde Erytheme und persistierende braune Hyperkeratosen. Vor kurzem wurde der zugrunde liegende Gendefekt der EKV auf dem kurzen Arm von Chromosom,1 lokalisiert, der für das Gap-Junction-Protein Connexin,31 kodiert. Wir stellen einen 48jährigen Patienten vor, bei dem seit dem dreißigsten Lebensjahr großflächige, scharf begrenzte, randständig schuppende Erytheme an den Extremitäten, Gesäß und Rumpf auftreten. Histologisch fand sich eine orthokeratotische Hyperkeratose mit fokaler Parakeratose bei Akanthose der Epidermis. Immunhistochemisch konnte eine vermindert Expression des Gap-Junction-Proteins Connexin,31 sowie vermehrte Expression von Connexin,43 dargestellt werden. Ultrastrukturell zeigten sich erweiterte Interzellularräume in der oberen Epidermis mit unauffälligen Desmosomen, Adherensjunktionen und regulären Gap Junctions. In der Epidermis wird u. a. die Zellproliferation und -differenzierung über die Gap Junctions reguliert. Die Mutation im Connexin,31 wird daher als ursächlich für das klinische Bild der EKV angesehen. Die Überexpression von Connexin,43, die hier erstmals beschrieben wird, entsteht möglicherweise reaktiv als Folge der CX31-Mutation und kompensiert vorübergehend den Defekt. Summary Erythrokeratodermia variabilis (EKV) is a rare autosomal dominant genodermatosis with disturbed epidermal differentiation. Its clinical picture varies from transient, fast moving erythema to persistent brown hyperkeratoses. The gene defect in EKV was recently located on the short arm of chromosome,1 encoding the gap junction protein connexin,31. We report on a 48-year-old patient with sharply circumscribed, scaling erythema on the extremities, buttocks and trunk starting since 30,years of age. Histological investigation showed orthokeratotic hyperkeratosis with focal parakeratosis overlying an acanthotic epidermis. Immunohistochemistry revealed a decreased expression of the gap junction protein connexin,31 as well as increased expression of connexin,43. At the ultrastructural level, widened intercellular spaces in the upper epidermis were present with regular desmosomes, adherens junctions and gap junctions. Epidermal cell proliferation and differentiation are regulated by gap junctions. The mutation in connexin,31 is regarded therefore as causal for the clinical picture of the EKV. The unique up-regulation of connexin,43 may occur as a consequence of the Cx31 mutation and temporarily compensate for this defect. [source] CD99 Immunoreactivity in Metastatic Malignant MelanomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005AE Wilkerson CD99, also known as p30/32, is a glycoprotein product of the MIC2 gene, which is located on the short arm of both chromosome X and Y. This transmembrane protein was originally utilized in immunohistochemistry as a unique marker for Ewing sarcoma, other primitive neuroectodermal tumors, and more recently in a wide variety of tumors. It's expression in malignant melanoma (MM) has not been well documented. A recent study at our institution demonstrated membranous staining in approximately 61% of primary MM. As CD99 is expressed by hematopoeitic cells, it has been proposed as a mechanism for lymphocytes to gain access to the vasculature.1 This study is designed to determine if CD99 expression in melanoma cells has a similar role using cases of metastatic MM from our archives. Our evaluation shows that 13 of 28 cases (46.4%) demonstrated membranous CD99 staining. A case of this magnitude has not been previously reported. Reference: 1. Shenkel AR, Mamdouh Z, Chen X, Liebman RM, Muller WA. CD99 plays a major role in the migration of monocytes through endothelial junctions. Nature Immunol 2002;3:143,150. [source] Genetic Analysis and Molecular Mapping of a Rolling Leaf Mutation Gene in RiceJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 12 2007Ji-Cai Yi Abstract A rice mutant with rolling leaf, namely ,- rl, was obtained from M2 progenies of a native indica rice stable strain Qinghuazhan (QHZ) from mutagenesis of dry seeds by ,-rays. Genetic analysis using the F2 population from a cross between this mutant and QHZ indicated the mutation was controlled by a single recessive gene. In order to map the locus for this mutation, another F2 population with 601 rolling leaf plants was constructed from a cross between ,- rl and a japonica cultivar 02428. After primary mapping with SSR (simple sequence repeats) markers, the mutated locus was located at the short arm of chromosome 3, flanked by RM6829 and RM3126. A number of SSR, InDel (insertion/deletion) and SNP (single nucleotide polymorphism) markers within this region were further developed for fine mapping. Finally, two markers, SNP121679 and InDel422395, were identified to be flanked to this locus with genetic distances of 0.08 cM and 0.17 cM respectively, and two SNP markers, SNP75346 and SNP110263, were found to be co-segregated with this locus. These results suggested that this locus was distinguished from all loci for the rolling leaf mutation in rice reported so far, and thus renamed rl10(t). By searching the rice genome database with closely linked markers using BLAST programs, an e -physical map covering rl10(t) locus spanning about a 50 kb region was constructed. Expression analysis of the genes predicted in this region showed that a gene encoding putative flavin-containing monooxygenase (FMO) was silenced in ,- rl, thus this is the most likely candidate responsible for the rolling leaf mutation. [source] Genetic Analysis and Mapping of the Dominant Dwarfing Gene D-53 in RiceJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 4 2006Li-Rong Wei Abstract The dwarfing gene D-53 is one of a few dominant genes for dwarfing in rice (Oryza sativa L.). In the present study, our genetic analysis confirmed that mutant characteristics including dwarfing, profuse tillering, thin stems and small panicles are all controlled by the dominant D-53 gene. We measured the length of each internode of KL908, a D-53- carrying line, and classified the dwarfism of KL908 into the dn-type. In addition, we measured elongation of the second sheath and ,-amylase activity in the endosperm, and we characterized KL908 as a dwarf mutant that was neither gibberellic acid-deficient nor gibberellic acid-insensitive. Using a large F2 population obtained by crossing KL908 with a wild-type variety, NJ6, the D-53 gene was mapped to the terminal region of the short arm of chromosome 11, with one simple sequence repeat marker, Ds3, co-segregating, and the other, K81114, located 0.6 cM away. (Managing editor: Li-Hui Zhao) [source] A new cytotype of Simulium squamosum from south-west CameroonMEDICAL AND VETERINARY ENTOMOLOGY, Issue 3 2004M. Mustapha Abstract., A new cytotype of Simulium squamosum Enderlein (Diptera: Simuliidae) (here named S. squamosum,D') is described from around Mount Cameroon in south-west Cameroon on the basis of sex-chromosome differences on the short arm of chromosome I. Two polymorphic inversions, IS-To (a new inversion) and IS-2, are partially Y linked. These inversions usually occur together, although IS-To has a higher frequency and is more strongly Y linked than IS-2. This sex-chromosome system has not been previously described and the occurrence and evolution of sex-chromosome systems in S. squamosum is discussed. [source] Karyotype analysis and physical mapping of 45S rRNA genes in Hydrangea species by fluorescence in situ hybridizationPLANT BREEDING, Issue 3 2008K. Van Laere Abstract Detailed karyotypes of Hydrangea macrophylla, Hydrangea paniculata and Hydrangea quercifolia were constructed on the basis of arm lengths and centromeric index, together with 45S rDNA fluorescence in situ hybridization. Although the chromosomes were small, they were well distinguishable for all species. Chromosome morphology and karyotypes were different for the three species. H. macrophylla had six metacentric (M), eight submetacentric (SM) and four subtelocentric (ST) chromosomes. The karyotype of H. paniculata contained seven M, 10 SM and one ST chromosomes and H. quercifolia had six M, 10 SM and two ST chromosomes. The variability among three species also was expressed by 45S rDNA signals. H. macrophylla had a nucleolar organizing region on chromosome 2, H. paniculata had 45S rDNA signals on chromosomes 2, 5 and 11 and H. quercifolia on chromosomes 3 and 8. Hybridization signal always was distally on the short arm but the strength of the signals was different for the three species. The chromosome portraits made in this study will be used to trace chromosome behaviour in interspecific hybrids resulting from breeding work between the three species. [source] Chromosomal location of powdery mildew resistance gene Pm16 in wheat using SSR marker analysisPLANT BREEDING, Issue 3 2005X. M. Chen Abstract The use of resistant cultivars is a most economical way to control powdery mildew (Blumeria graminis f.sp. tritici) in wheat (Triticum aestivum L.). Identification of molecular markers closely linked to resistance genes can greatly increase the efficiency of pyramiding resistance genes in wheat cultivars. The objective of this study was to identify molecular markers closely linked lo the powdery mildew resistance gene Pm16. An F2 population with 156 progeny was produced from the cross,Chancellor'(susceptible) ×,70281' (resistant), A total of 45 SSR markers on chromosomes 4A and 5B of wheat and 15 SSRs on chromosome 3 of rice was used lo lest the parents, as well as the resistant and susceptible bulks: the resulting polymorphic markers were used to genotype the F2 progeny. Results indicated that the SSR marker Xgwm159, located on the short arm of chromosome 5B, is closely linked to Pm16 (genetic distance: 5.3 CM). The cytogenetical data presented in an original report, in combination with this molecular analysis, suggests that Pm16 may he located on a translocated 4A.5BS chromosome. [source] The study of introgressive lines of Triticum aestivum × Aegilops speltoides by in situ and SSR analysesPLANT BREEDING, Issue 3 2004I. G. Adonina Abstract Fluorescence in situ hybridization (FISH) with a genome-specific repeat, Spelt1, and wheat simple sequence repeat (SSR) markers were used to analyse the chromosome constitution of two Triticum aestivum×Aegilops speltoides introgressive lines. The lines 170/98i and 178/98i carried one and two subtelomeric regions of Ae. speltoides (per haploid genome), respectively, marked by Spelt1 repeats according to FISH data. SSR analysis detected homoeologous substitution of wheat chromosome 7D with Ae. speltoides chromosome 7S in the lines 178/98i and 170/98i as well as the assumed terminal translocation in the short arm of chromosome 3A in the line 178/98i. Anthocyanin pigmentation of the coleoptiles was found in the lines 170/98i and 178/98i and resulted from the 7S (7D) substitution. It was demonstrated that Spelt1 could be effectively used for the rapid identification (without DNA isolation) of terminal translocations of T. aestivum×Ae. speltoides introgressive lines as well as for further analysis of the stability of the hybrid plants. [source] Cytogenetical studies in wheat.PLANT BREEDING, Issue 1 2000XVIII. Abstract A new gene, Yr24, for resistance to stripe rust was transferred from a durum accession to common wheat via an amphiploid (synthetic wheat) with Aegilops tauschii. Yr24 was located in chromosome 1B by monosomic analysis. Its genetic linkage of 4 cM with Yr15 indicated its localization to the short arm. [source] Diagnostic yield by supplementing prenatal metaphase karyotyping with MLPA for microdeletion syndromes and subtelomere imbalancesPRENATAL DIAGNOSIS, Issue 10 2010S. Kjaergaard Abstract Objective The aim of the study was to retrospectively assess the relevance of using multiplex ligation-dependent probe amplification (MLPA) for detection of selected microdeletion syndromes (22q11, Prader,Willi/Angelman, Miller,Dieker, Smith,Magenis, 1p-, Williams), the reciprocal microduplication syndromes and imbalance at the subtelomere regions of chromosomes in a routine prenatal setting. Method A total of 530 prenatal samples were analysed by commercial MLPA kits (SALSA P064, P036 and P069) in addition to rapid aneuploidy testing and G-band karyotyping. Results Among the prenatal samples with a normal metaphase karyotype, nine submicroscopic imbalances were detected: seven 22q11 deletions (Velocardiofacial/DiGeorge syndrome), one 15q11deletion (Prader,Willi syndrome) and one terminal deletion of the short arm of chromosome 4 (Wolf,Hirschhorn syndrome). All imbalances were found in amniocentesis (AC) taken due to fetal structural malformation and/or other ultrasound scan (US) detected abnormality. The diagnostic yield was 4.1% in the subgroup with structural malformation and 1.6% in the subgroup with other US abnormality. Conclusion The data set substantiates that additional MLPA analyses for selected microdeletions and subtelomere imbalances are valuable in routine prenatal diagnostics, when a malformation(s) and/or other abnormalities are detected by US. In contrast, the additional MLPA analyses gave no diagnostic yield in case of increased nuchal translucency (NT). Copyright © 2010 John Wiley & Sons, Ltd. [source] A short history of the initial discovery of the Wolf,Hirschhorn syndrome,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 4 2008Kurt Hirschhorn Abstract Deletion of the short arm of chromosome 4 (4p-) was first described in 1961 [Hirschhorn and Cooper, 1961], and the second case of 4p- was published in 1965 [Hirschhorn et al., 1965]. This short history describes the original case and the sequence of events leading to the publications. © 2008 Wiley-Liss, Inc. [source] Update on the clinical features and natural history of Wolf,Hirschhorn (4p-) syndrome: Experience with 87 patients and recommendations for routine health supervision,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 4 2008Agatino Battaglia Abstract Wolf,Hirschhorn syndrome (WHS) is a well-known multiple congenital anomalies/mental retardation syndrome, firstly described in 1961 by Cooper and Hirschhorn. Its frequency is estimated as 1/50,000,1/20,000 births, with a female predilection of 2:1. The disorder is caused by partial loss of material from the distal portion of the short arm of chromosome 4 (4p16.3), and is considered a contiguous gene syndrome. No single gene deletions or intragenic mutations have been shown to confer the full WHS phenotype. Since the disorder was brought to the attention of geneticists, many additional cases have been published. Only in 1999, however, were the first data on the natural history brought to the attention of the medical community. The purpose of the present study is to help delineate in more detail and over a longer period of time, the natural history of WHS, in order to establish appropriate health supervision and anticipatory guidance for individuals with this disorder. We have collected information on 87 patients diagnosed with WHS (54 females and 33 males) both in USA and Italy. Age at first observation ranged between newborn and 17 years. Twenty patients have been followed from 4 months to 23 years. The deletion proximal breakpoint varied from 4p15.32 to 4p16.3, and, by FISH, was terminal and included both WHSCR. Deletion was detected by standard cytogenetics in 44/87 (50.5%) patients, whereas FISH was necessary in the other 43 (49.5%). Array-CGH analysis at 1 Mb resolution was performed in 34/87 patients, and, in 15/34 (44%), showed an unbalanced translocation leading to both a 4p monosomy and a partial trisomy for another chromosome arm. Six more patients had been previously shown to have an unbalanced translocation by karyotype analysis or FISH with a WHS-specific probe. Sixty-five of 87 patients had an apparent pure, de novo, terminal deletion; and 1/87 a tandem duplication of 4p16.1p16.3 associated with 4p16.3pter deletion. Age at diagnosis varied between 7 months gestation and 16 years. Ninety-three percent had a seizure disorder with a good outcome; 80% had prenatal onset growth deficiency followed by short stature and slow weight gain; 60% had skeletal anomalies; 50% had heart lesions; 50% had abnormal tooth development; and 40% had hearing loss. Distinctive EEG findings were seen in 90%. Structural CNS anomalies were detected in 80%. Global developmental delay of varying degrees was present in all patients. Almost 50% was able to walk either alone or with support. Hypotonia was present in virtually all patients. A global improvement was observed in all individuals, over time. Our survey has also shown how the characteristic facial phenotype tends to be less pronounced in those patients with a smaller deletion, and microcephaly is not observed in the patients with certain cryptic unbalanced translocations. © 2008 Wiley-Liss, Inc. [source] Prenatal detection of complex chromosomal aberrations using advanced molecular cytogenetic techniquesPRENATAL DIAGNOSIS, Issue 9 2003J. M. de Pater Abstract Objective This study aimed to identify a marker chromosome and characterize the short arm of a derivative chromosome 5 in a foetus with the following karyotype: mos 47,XX,del(5)(p?),+i(5)(p10)[50]/48,XX,del(5)(p?),+i(5)(p10),+mar[25]. Method Amniocentesis was performed in the 26th week of pregnancy because of ultrasound abnormalities (polyhydramnion and decreased amount of gastric filling). All classic banding techniques were performed. FISH and microdissection combined with reverse painting were used to reveal the exact origin of the marker and any extra material on the deleted chromosome 5p. The parents decided to continue the pregnancy and we compared the clinical features of the child born in week 34 with data from the literature on trisomy 5p. The possible contribution of trisomy of the centromeric region of chromosome 8 and trisomy 8p23.3,8pter to this clinical picture was evaluated. Results GTG banding showed one normal and two aberrant chromosomes 5 [del(5)(p?) and i(5)(p10)] in all the cells examined. Furthermore, a supernumerary marker chromosome was present in approximately 30% of the cells. The marker was CBG positive and positive with the pancentromere probe, but dystamicinA/DAPI negative. It did not contain NOR-positive satellites. FISH proved this marker to be derived from the centromeric region of chromosome 8. MicroFISH disclosed the aberrant chromosome 5 as der(5)t(5;8)(p10;p23.3). The parent's karyotypes were normal. The baby showed the characteristic features of trisomy 5p syndrome. She died at the age of 15 days after cardiorespiratory arrest. Conclusion The karyotype was interpreted as mos 47,XX,add(5)(p10).rev ish der(5)t(5;8)(p10;p23.3),+i(5)(p10) (WCP5+,D5S23+)[50]/48,XX,add(5)(p10).rev ish der(5)t(5;8)(p10;p23.3),+i(5)(p10)(WCP5+,D5S23+),+mar.ish 8(p10q10)(D8Z2+,WCP8-)[25]. Therefore, the baby had complete trisomy 5p, with trisomy of the distal part of 8p and of the centromeric region of chromosome 8. The clinical significance of de novo marker chromosomes is a major problem in prenatal counselling. Molecular cytogenetic tools such as FISH and microFISH are indispensable for characterizing markers and determining the breakpoints more precisely in deleted chromosomes. Copyright © 2003 John Wiley & Sons, Ltd. [source] A familial Xp+ chromosome detected during fetal karyotyping, which is associated with short stature in four generations of a Turkish familyPRENATAL DIAGNOSIS, Issue 4 2003B. Karaman Abstract The short-stature homeobox-containing gene (SHOX) on chromosome Xp22.3 was recently identified as an important determinant of the stature phenotype. Deletions of the SHOX gene, some of them due to structural chromosome abnormalities, have been described in patients with idiopathic short stature and Leri-Weill syndrome. Additionally, haploinsufficiency of SHOX is a main cause for short stature seen in patients with Turner syndrome. Here we report an unusual X-chromosome abnormality, which was detected during a fetal karyotyping performed because of a previous child with Down syndrome. GTG banding demonstrated an extra chromosome segment on the terminal part of the short arm of chromosome X in the index case (karyotype: 46,X,Xp+). The same chromosomal abnormality was found in the mother and the maternal grandmother. All carriers of this chromosomal abnormality presented with short stature but no other associated symptoms. Whole chromosome painting of X revealed a homogeneous painting of the abnormal X chromosome indicating that no other chromosome was involved. Additional FISH studies with probe DXS1140 (Kallmann probe at Xp22.3), Quint-Essential X-Specific DNA (DMD probe at Xp21.2), XIST (at Xq13.2), and Tel Xq/Yq were performed, and no abnormality was observed in the intensities or the localizations of the probes signals. However, applying a specific SHOX gene probe (derived from cosmid LLNONO3M34F5) showed a loss of signal on the derivative X chromosome. Our results show that the Xp+ generation led to a deletion of the complete SHOX gene and caused short stature in the presented family. Copyright © 2003 John Wiley & Sons, Ltd. [source] A case of intersexuality in pigs associated with a de novo paracentric inversion 9 (p1.2; p2.2)ANIMAL GENETICS, Issue 1 2002A. Pinton In several mammalian species, genetic defects can be responsible for the interruption of and/or the deviation from the sequential steps of normal gonadal differentiation, leading to a sex-reversal syndrome. In pigs, female-to-male sex-reversal conditions are particularly frequent, but their aetiologies remain unclear. Chromosomal abnormalities that co-occur with sex-reversal disorders can be useful in the identification of loci containing responsible or susceptibility genes. This report describes a female-to-male SRY -negative intersex pig with a de novo paracentric inversion of the short arm of one chromosome 9 (p1.2; p2.2). We have fine mapped the proximal chromosomal breakpoint of this rearrangement because it corresponded to a region potentially involved in the pig intersexuality. Fluorescent in situ hybridization (FISH) experiments carried out with Bacterial Artificial Chromosome (BAC) clones located within the critical region defined by genetic linkage analysis and ordered on the porcine RH map allowed us to locate the proximal breakpoint between markers SW2571 and SW539. Further investigations are currently in progress to find new markers inside this interval, in order to determine the BAC in which the break occurred. [source] Mapping of powdery mildew resistance genes in a newly determined accession of Hordeum vulgare ssp. spontaneumANNALS OF APPLIED BIOLOGY, Issue 2 2010K. Teturová The accession PI466197 of wild barley (Hordeum vulgare ssp. spontaneum) with a newly identified resistance to powdery mildew caused by Blumeria graminis f.sp. hordei was studied with the aim to localise the genes determining resistance on a barley genetic map using DNA markers. Molecular analysis was performed in the F2 population of the cross between the winter variety ,Tiffany' and the resistant accession PI466197, consisting of 113 plants. DNA markers, 17 simple sequence repeats (SSRs), four sequence-tagged sites (STSs) and one cleaved amplified polymorphic sequence (CAPS) marker developed from the Mla locus sequence were used for genetic mapping and a two-locus model of resistance was shown. One of the resistance genes originating from H. vulgare ssp. spontaneum PI466197 was localised between the markers RGH1aE1 and Bmac0213 on the short arm of chromosome 1H, which is the position consistent with the Mla locus. The other gene was proven to be highly significantly linked with GBMS247, Bmac0134 and MWG878 on the short arm of chromosome 2H. The flanking markers were Bmac0134 and MWG878, assigned 4 and 8 cM from the resistance gene, respectively. Until now, no gene conferring powdery mildew resistance originating from H. vulgare has been located on the short arm of barley chromosome 2H. [source] Chromosome studies in Hippeastrum (Amaryllidaceae): variation in genome sizeBOTANICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 2 2007LIDIA POGGIO This paper presents the karyotype and DNA content of 12 diploid species of Hippeastrum from South America. The variation in genome size is compared with the karyotype and DNA content of Amaryllis belladonna from South Africa. The Hippeastrum species present a uniform and bimodal basic karyotype formula, but significant differences are found in the total chromosome volume (TCV) and nuclear DNA content. A positive correlation between the DNA content and TCV is also observed. The karyotype's constancy is a product of changes in DNA content occurring in the whole chromosome complement. The DNA addition to the long and short sets of chromosomes varies independently. In species with higher DNA contents, the short chromosomes add equal DNA amounts to both arms, maintaining their metacentric morphology, whereas the long chromosomes add DNA only to the short arm, increasing the chromosome symmetry. These data show that the evolutionary changes in DNA amount are proportional to chromosome length, maintaining the karyotypic uniformity. A. belladonna has a larger DNA content and possesses a karyotype different from that of Hippeastrum spp., supporting the distinction between the two genera and upholding the name Amaryllis for the South African entity against Hippeastrum for the South American genus. © 2007 The Linnean Society of London, Botanical Journal of the Linnean Society, 2007, 155, 171,178. [source] A non-sense mutation in the corneodesmosin gene in a Mexican family with hypotrichosis simplex of the scalpBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2005N.O. Dávalos Summary Background, Hypotrichosis simplex of the scalp (HSS; MIM 146520) is a rare autosomal dominant form of non-syndromic alopecia that affects men and women equally. Up to now, only a small number of families with HSS have been reported. The affected individuals experience a diffuse progressing hair loss from childhood to adulthood that is confined to the scalp. Recently, HSS has been mapped to the short arm of chromosome 6 (6p21.3), allowing mutations in the corneodesmosin gene (CDSN) to be identified as the cause of the disorder. To date, two stop mutations have been found in three unrelated families with HSS of different ethnic origin. Objectives, To describe the first HSS-family with Latin American (Mexican) background comprising 6 generations and to identify a mutation in the CDSN gene. Patients/Methods, The patients were examined by a clinician and blood samples were taken. After DNA extraction, sequencing analysis of the CDSN gene and restriction enzyme analysis with PsuI were performed. Results, By direct sequencing of the two exons of the CDSN gene, a nonsense mutation was identified in the index patient in exon 2, resulting in a premature stop codon (Y239X). The mutation cosegregates perfectly in the family with the disease and was not found in 300 control chromosomes using a restriction enzyme analysis with PsuI. Conclusions, A nonsense mutation was identified in the first family with HSS of Latin American ethnical background. Our data provide molecular genetic evidence for a 3rd stop mutation in exon 2 of the CDSN gene being responsible for HSS. All to date known nonsense mutations responsible 3 for HSS are clustered in a region of 40 amino acids which is in accordance with a dominant negative effect conferred by aggregates of truncated CDSN proteins. [source] Translocations involving 6p22 in acute myeloid leukaemia at relapse: breakpoint characterization using microarray-based comparative genomic hybridizationBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2004Joëlle Tchinda Summary The detection of chromosomal aberrations is essential for the diagnosis and therapy of acute myeloid leukaemia (AML). We report two cases of de novo AML with translocations involving the breakpoint 6p22 first detected at relapse. Chromosomes were identified by conventional and molecular cytogenetics. At diagnosis, one patient presented a normal karyotype and the other one a trisomy 11 and a del(7)(q31q36). In the first case, cytogenetic analyses at relapse revealed a t(3;6)(q21;p22). The second patient showed a t(1;6)(q21;p22) at relapse. Detailed characterization of the breakpoints on the short arm of chromosome 6 was performed using array comparative genomic hybridization (CGH) on a platform specific for chromosome 6. In both cases, array CGH showed a terminal deletion and a small internal duplication of the short arm of chromosome 6. The region 6p22 is involved in several aberrations in tumours. Translocation partners are distributed throughout the human genome. We identified 3q21, a recurrent breakpoint in AML, for the first time as a translocation partner. The fragile site FRA6C, located in 6p22.2, and possibly the genes that reside within it, may play a role in tumorigenesis. The occurrence of translocations involving 6p22 after chemotherapy or radiation therapy suggests that one or more therapeutic agents might play a role in their origin. [source] De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic featuresCLINICAL GENETICS, Issue 2 2010P Makrythanasis Makrythanasis P, Moix I, Gimelli S, Fluss J, Aliferis K, Antonarakis SE, Morris MA, Béna F, Bottani A. De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic features. Loss-of-function mutations of MECP2 are responsible for Rett syndrome (RTT), an X-linked neurodevelopmental disorder affecting mainly girls. The availability of MECP2 testing has led to the identification of such mutations in girls with atypical RTT features and the recognition of milder forms. Furthermore, duplication of the entire gene has recently been described in boys with mental retardation and recurrent infections. We describe a girl with a heterozygous de novo MECP2 duplication. The patient, at the age of 19, has mental retardation with no autistic features. She is friendly but gets frequently anxious. She has neither dysmorphic features nor malformations. Her motor development was delayed with walking at 20 months. Speech is fluid with good pronunciation but is simple and repetitive. Diagnosis was made after single-strand conformation analysis (SSCA) and multiplex ligation-dependent probe amplification (MLPA) analysis of MECP2. Array comparative genomic hybridization (aCGH) analysis showed a duplication of 29 kb including MECP2 and part of IRAK1. Fluorescent in situ hybridization (FISH) has revealed that the duplicated region is inserted near the telomere of the short arm of chromosome 10. X-chromosome inactivation in leukocyte DNA was not skewed. We conclude that it is likely that this MECP2 duplication is responsible for the mental retardation in this patient. This case broadens the phenotypic spectrum of MECP2 abnormalities with consequent implication in diagnosis and genetic counselling of girls with non-syndromic mental retardation. [source] | |||||||||||||