Molecular Study (molecular + study)

Distribution by Scientific Domains


Selected Abstracts


Compound heterozygosity of Hb DIran (,22 Glu,Gln) and ,0 -thalassemia (619 bp-deletion) in India

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2007
Meenal G. Agrawal
Abstract The present report describes the hematologic and molecular study of the second case of Hb DIran associated with ,0 -thalassemia (619 bp-deletion) found in India and the first case in which the mutations have been identified at molecular level. The patient showed hypochromic, microcytic red cell picture with reduced red cell indices. The characterization of the hemoglobinopathy was made by electrophoretic and chromatographic techniques and confirmed by sequencing of the beta-globin gene. Both the propositus and her father were found to be carriers of the gene for ,0 -thalassemia owing to the 619 bp-deletion mutation as seen by the polymerase chain reaction (PCR). Single base substitution GAA > CAA (indicative of Hb DIran) in the heterozygous form was seen in the propositus as well as the mother by sequencing. [source]


Robust support for tardigrade clades and their ages from three protein-coding nuclear genes

INVERTEBRATE BIOLOGY, Issue 2 2004
Jerome C. Regier
Abstract. Coding sequences (5,334 nt total) from elongation factor-1,, elongation factor-2, and the largest subunit of RNA polymerase II were determined for 6 species of Tardigrada, 2 of Arthropoda, and 2 of Onychophora. Parsimony and likelihood analyses of nucleotides and amino acids yielded strong support for Tardigrada and all internal nodes (i.e., 100% bootstrap support for Tardigrada, Eutardigrada, Parachela, Hypsibiidae, and Macrobiotidae). Results are in agreement with morphology and an earlier molecular study based on analysis of 18S ribosomal sequences. Divergence times have been estimated from amino acid sequence data using an empirical Bayesian statistical approach, which does not assume a strict molecular clock. Divergence time estimates are pre-Vendian for Tardigrada/Arthropoda, Vendian or earlier for Eutardigrada/Heterotardigrada, Silurian to Ordovician for Parachela/Apochela, Permian to Carboniferous for Hypsibiidae and Macrobiotidae, and Mesozoic for Isohypsibius/Thulinia (both within Hypsibiidae) and Macrobiotus/Richtersius (both within Macrobiotidae). [source]


Comparison of DNA- and RNA-based bacterial community structures in soil exposed to 2,4-dichlorophenol

JOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2009
L. Lillis
Abstract Aims:, To examine the effect of the pollutant 2,4-dichlorophenol on DNA- and RNA-based bacterial communities in soil. Methods and Results:, Soil was exposed to 100 mg kg,1 of 2,4-dichlorophenol (2,4-DCP), and degradation was monitored over 35 days. DNA and RNA were coextracted, and terminal restriction fragment length polymorphism (T-RFLP) was used to report changes in bacterial communities in response to the presence of the chlorophenol. The phylogenetic composition of the soil during degradation was determined by creating a clone library of amplified 16S rRNA sequences from both DNA and reverse-transcribed RNA from exposed soil. Resulting clones were sequenced, and putative identities were assigned. Conclusions:, A significant difference between active (RNA-based) and total (DNA-based) bacterial community structure was observed for both T-RFLP and phylogenetic analyses in response to 2,4-DCP, with more pronounced changes seen in RNA-based communities. Phylogenetic analysis indicated the dominance of Proteobacteria in both profiles. Significance and Impact of the Study:, This study describes the response of soil bacterial communities to the addition of the xenobiotic compound 2,4-DCP, and highlights the importance of including RNA-based 16S rRNA analysis to complement any molecular study in a perturbed soil. [source]


Mechanisms of pathogenesis and the evolution of parasite virulence

JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 2 2008
S. A. FRANK
Abstract When studying how much a parasite harms its host, evolutionary biologists turn to the evolutionary theory of virulence. That theory has been successful in predicting how parasite virulence evolves in response to changes in epidemiological conditions of parasite transmission or to perturbations induced by drug treatments. The evolutionary theory of virulence is, however, nearly silent about the expected differences in virulence between different species of parasite. Why, for example, is anthrax so virulent, whereas closely related bacterial species cause little harm? The evolutionary theory might address such comparisons by analysing differences in tradeoffs between parasite fitness components: transmission as a measure of parasite fecundity, clearance as a measure of parasite lifespan and virulence as another measure that delimits parasite survival within a host. However, even crude quantitative estimates of such tradeoffs remain beyond reach in all but the most controlled of experimental conditions. Here, we argue that the great recent advances in the molecular study of pathogenesis provide a way forward. In light of those mechanistic studies, we analyse the relative sensitivity of tradeoffs between components of parasite fitness. We argue that pathogenic mechanisms that manipulate host immunity or escape from host defences have particularly high sensitivity to parasite fitness and thus dominate as causes of parasite virulence. The high sensitivity of immunomodulation and immune escape arise because those mechanisms affect parasite survival within the host, the most sensitive of fitness components. In our view, relating the sensitivity of pathogenic mechanisms to fitness components will provide a way to build a much richer and more general theory of parasite virulence. [source]


HTLV-1 infection in blood donors from the Western Brazilian Amazon region: Seroprevalence and molecular study of viral isolates

JOURNAL OF MEDICAL VIROLOGY, Issue 11 2008
Aline Cristina Mota-Miranda
Abstract To determine the seroprevalence of HTLV-1 in Brazil, and to review the virus molecular epidemiology in this Amazon population (Rio Branco-Acre), 219 blood donors were screened for HTLV-1. Only one case of infection (0.46% seroprevalence) was detected during July 2004 screening at the Acre Hospital Foundation (FUNDACRE). Neighbor-joining and Maximum Likelihood phylogenetic analyses of two (n,=,2) complete LTR region sequences were performed with the PAUP* software. Since the HTLV-1 envelope surface (gp46) and transmembrane (gp21) glycoproteins are important for virus fitness, three envelope glycoproteins sequences (n,=,3) were analyzed using the Prosite tool to determinate potential protein sites. Phylogenetic analysis demonstrated that the new isolate described in this study, and the unpublished LTR strain described in a previous report belong to the Transcontinental subgroup of the Cosmopolitan subtype, inside the Latin American cluster. A similar result was obtained when submitting, to the Automated Genotyping System, three LTR partial sequences from a previous study of the seroprevalence of HTLV-1 in the same Amazon population. In all analyzed env sequences, the potential protein site was found: two PKC phosphorylation sites at amino acid (aa) positions 310,312 and 342,344, one CK2 phosphorylation site at 194,197aa, three N -glycosylation sites at 222,225aa, 244,247aa and 272,275aa, and a single N -myristylation site at 327,338aa. In conclusion, potential protein sites described in HTLV-1 gp46 and gp21 confirm the presence of conserved sites in the HTLV-1 envelope proteins, likewise phylogenetic analysis suggests a possible recent introduction of the virus into North Brazil. J. Med. Virol. 80:1966,1971, 2008. © 2008 Wiley-Liss, Inc. [source]


TAXONOMY OF THE NEW ZEALAND-ENDEMIC GENUS PLEUROSTICHIDIUM (RHODOMELACEAE, RHODOPHYTA)

JOURNAL OF PHYCOLOGY, Issue 4 2000
Louise E. Phillips
A morphological, anatomical, and molecular study of the tribe Pleurostichidieae (Rhodomelaceae, Ceramiales) is presented. New collections of its only member, Pleurostichidium falkenbergii Heydrich, have enabled a thorough re-assessment of this species from a classical-morphological standpoint and have allowed the first photographs to be made of critical features of this little-known obligate epiphyte of the brown alga Xiphophora chondrophylla (Turner) Montagne ex Harvey. The relationship of the tribe to other members of the Rhodomelaceae is considered based on analysis of 18S rDNA sequences from P. falkenbergii, 14 other rhodomelaceous species, and six outgroup taxa. Pleurostichidium falkenbergii is shown to be most closely related to the tribe Polysiphonieae and only distantly related to the Amansieae, with which it was previously associated. [source]


Chordate phylogeny and evolution: a not so simple three-taxon problem

JOURNAL OF ZOOLOGY, Issue 2 2008
T. Stach
Abstract Traditional concepts of chordate phylogeny have recently been in turmoil: in a large-scale molecular study, the traditional hypothesis that cephalochordates are sister taxon to craniates was replaced by the hypothesis of a sister group relationship between tunicates and craniates. It was claimed that the morphological evidence that supported traditional phylogeny was weak and that morphological characters at least equally strong could be mustered in support of the ,new phylogeny.' In the present review, it is shown that the uncritical use of published codings of morphological characters in recent phylogenetic analyses is responsible for this perception. To ameliorate this situation, the main focus of the present publication is a review of the morphological evidence that has been deemed relevant in chordate phylogeny. Characters are presented in enough detail to allow readers to make self-reliant informed decisions on character coding. I then analyze these characters cladistically, and it is demonstrated that support of the traditional hypothesis is substantial. I briefly evaluate molecular systematic studies and criticize ,evo-devo' studies for lack of cladistic rigor in the evolutionary interpretations of their data by (1) failing to formally code their characters (2) failing to subject their data to the congruence test with other characters, the crucial test in phylogenetic analyses. Finally, a short and by necessity eclectic discussion of suggested evolutionary scenarios is presented. [source]


Phylogeny of the subgenus Culicoides and related species in Italy, inferred from internal transcribed spacer 2 ribosomal DNA sequences

MEDICAL AND VETERINARY ENTOMOLOGY, Issue 2 2006
L. M. Gomulski
Abstract., Biting midges of the genus Culicoides (Diptera: Ceratopogonidae) include vectors for the economically important animal diseases, bluetongue (BT) and African horse sickness (AHS). In the Mediterranean Basin, these diseases are transmitted by four species of Culicoides: the first three belong in the subgenus Avaritia Fox and are Culicoides imicola Kieffer, Culicoides obsoletus (Meigen) and Culicoides scoticus Downes and Kettle; the fourth is Culicoides pulicaris (Linnaeus) in the subgenus Culicoides Latreille. In the Palaearctic Region, this subgenus (usually referred to as the C. pulicaris group) now includes a loose miscellany of some 50 taxa. The lack of clarity surrounding its taxonomy stimulated the present morphological and molecular study of 11 species collected in Italy. Phylogenetic analysis of nuclear ribosomal DNA internal transcribed spacer 2 (ITS2) sequence variation demonstrated a high degree of divergence. These results, combined with those from a parallel morphological study, disclosed: (1) that some previously described taxa should be resurrected from synonymy; (2) that there are new species to be described; (3) that the subgenus Culicoides (as currently employed) is a polyphyletic assemblage of four lineages , the subgenus Culicoides sensu stricto, the subgenus Silvicola Mirzaeva and Isaev, the subgenus Hoffmania Fox and the hitherto unrecognized Fagineus species complex. Each is discussed briefly (but not defined) and its constituent Palaearctic taxa listed. Strong congruence between morphological and molecular data holds promise for resolving many of the difficult taxonomic issues plaguing the accurate identification of vector Culicoides around the world. [source]


A host-vector system for molecular study of the intracellular growth of Mycobacterium tuberculosis in phagocytic cells

MICROBIOLOGY AND IMMUNOLOGY, Issue 10 2009
Mari Nomoto
ABSTRACT The mechanisms by which Mycobacterium tuberculosis survives and persists in phagocytic cells remain poorly understood. To study the question, a convenient and safe host-vector system is indispensable. In this study it has been shown that, in contrast with M. smegmatis strain mc2155 which has been widely used for molecular analysis, M. smegmatis strain J15cs is able to survive even at day 6 post-infection in a murine macrophage cell line, J774. The survivability of J15cs was found to depend on the culture medium used for the bacteria prior to infection. Bacteria precultured on nutrient agar medium showed a high survivability and a characteristic cell wall ultrastructure. A plasmid vector, pYT923hyg, was developed from an Escherichia coli - mycobacterium shuttle vector pYT923 (previously constructed in our laboratory) to obtain three drug resistant genes (amp-, hyg- and km-resistant gene) and cloning sites in the km resistant gene. The vector pYT923hyg exerted no influence on in vitro growth of J15cs and intracellular survival in J774 cells, and was stably retained in J15cs after serial subculturing (three subcultures) in Luria-Bertani broth and at day 5 post-infection into J774 cells. Furthermore, using this system, the possibility of a relationship between some seemingly essential genes of M. tuberculosis and intracellular growth was demonstrated. In this study, M. smegmatis strain J15cs and pYT923hyg were found to be capable of serving as an appropriate host-vector system for molecular study of the intracellular growth of M. tuberculosis in phagocytic cells; this system may be useful as a screening tool for M. tuberculosis genes. [source]


Mating system, philopatry and patterns of kinship in the cooperatively breeding subdesert mesite Monias benschi

MOLECULAR ECOLOGY, Issue 11 2005
N. SEDDON
Abstract In the first molecular study of a member of the threatened avian family, Mesitornithidae, we used nine polymorphic microsatellite loci to elucidate parentage, patterns of within-group kinship and occurrence of extra-group paternity in the subdesert mesite Monias benschi, of southwest Madagascar. We found this cooperatively breeding species to have a very fluid mating system. There was evidence of genetic monogamy and polygynandry: of the nine groups with multiple offspring, six contained one breeding pair with unrelated helpers and three contained multiple male and female breeders with related helpers. Although patterns of within-group kinship varied, there was a strong positive relationship between group size and relatedness, suggesting that groups form by natal philopatry. There was also a strong positive correlation between within-sex and between-sex relatedness, indicating that unlike most cooperatively breeding birds, philopatry involved both sexes. In contrast to predictions of kin selection and reproductive skew models, all monogamous groups contained unrelated individuals, while two of the three polygynandrous groups were families. Moreover, although between-group variation in seasonal reproductive success was related to within-group female relatedness, relatedness among males and between the sexes had no bearing on a group's reproductive output. While kin selection may underlie helping behaviour in females, factors such as direct long-term fitness benefits of group living probably determine helping in males. Of the 14 offspring produced by fully sampled groups, at least two were sired by males from neighbouring groups: one by a breeding male and one by a nonbreeding male, suggesting that males may augment their reproductive success through extra-group paternity. [source]


Mitochondrial DNA and microsatellite variation in the eider duck (Somateria mollissima) indicate stepwise postglacial colonization of Europe and limited current long-distance dispersal

MOLECULAR ECOLOGY, Issue 6 2004
R. Tiedemann
Abstract To unravel the postglacial colonization history and the current intercolony dispersal in the common eider, Somateria mollissima, we analysed genetic variation at a part of the mitochondrial control region and five unlinked autosomal microsatellite loci in 175 eiders from 11 breeding colonies, covering the entire European distribution range of this species. As a result of extreme female philopatry, mitochondrial DNA differentiation is substantial both among local colonies and among distant geographical regions. Our study further corroborates the previous hypothesis of a single Pleistocene refugium for European eiders. A nested clade analysis on mitochondrial haplotypes suggests that (i) the Baltic Sea eider population is genetically closest to a presumably ancestral population and that (ii) the postglacial recolonization progressed in a stepwise fashion via the North Sea region and the Faroe Islands to Iceland. Current long-distance dispersal is limited. Differentiation among colonies is much less pronounced at microsatellite loci. The geographical pattern of this nuclear genetic variation is to a large extent explained by isolation by distance. As female dispersal is very limited, the geographical pattern of nuclear variation is probably explained by male-mediated gene flow among breeding colonies. Our study provides genetic evidence for the assumed prominent postglacial colonization route shaping the present terrestrial fauna of the North Atlantic islands Iceland and the Faroes. It suggests that this colonization had been a stepwise process originating in continental Europe. It is the first molecular study on eider duck populations covering their entire European distribution range. [source]


Botrytis cinerea: the cause of grey mould disease

MOLECULAR PLANT PATHOLOGY, Issue 5 2007
BRIAN WILLIAMSON
SUMMARY Introduction:,Botrytis cinerea (teleomorph: Botryotinia fuckeliana) is an airborne plant pathogen with a necrotrophic lifestyle attacking over 200 crop hosts worldwide. Although there are fungicides for its control, many classes of fungicides have failed due to its genetic plasticity. It has become an important model for molecular study of necrotrophic fungi. Taxonomy:, Kingdom: Fungi, phylum: Ascomycota, subphylum: Pezizomycotina, class: Leotiomycetes, order: Helotiales, family: Sclerotiniaceae, genus: Botryotinia. Host range and symptoms: Over 200 mainly dicotyledonous plant species, including important protein, oil, fibre and horticultural crops, are affected in temperate and subtropical regions. It can cause soft rotting of all aerial plant parts, and rotting of vegetables, fruits and flowers post-harvest to produce prolific grey conidiophores and (macro)conidia typical of the disease. Pathogenicity:,B. cinerea produces a range of cell-wall-degrading enzymes, toxins and other low-molecular-weight compounds such as oxalic acid. New evidence suggests that the pathogen triggers the host to induce programmed cell death as an attack strategy. Resistance:, There are few examples of robust genetic host resistance, but recent work has identified quantitative trait loci in tomato that offer new approaches for stable polygenic resistance in future. Useful websites:,http://www.phi-base.org/query.php, http://www.broad.mit.edu/annotation/genome/botrytis_cinerea/Home.html, http://urgi.versailles.inra.fr/projects/Botrytis/, http://cogeme.ex.ac.uk [source]


Genetic heterogeneity in patients with pantothenate kinase,associated neurodegeneration and classic magnetic resonance imaging eye-of-the-tiger pattern

MOVEMENT DISORDERS, Issue 2 2006
Paola Valentino MD
Abstract We performed a detailed molecular study in two unrelated families with pantothenate kinase,associated neurodegeneration (PKAN) and the specific magnetic resonance imaging (MRI) eye-of-the-tiger pattern. In the first family with classic PKAN, linkage analysis using polymorphic markers from the PANK2 region ruled out linkage with this locus, and no mutation of the PANK2 gene was found. In the second family with atypical PKAN, we identified a novel homozygous C-to-T transition at nucleotide 1069 of the PANK2 gene, which resulted in an arginine to tryptophane substitution at codon 357. As far as we are aware, this is the first case of classic PKAN with the specific MRI eye-of-the-tiger pattern not carrying a PANK2 mutation. Therefore, the present observation reinforces the notion of the phenotypic and genetic heterogeneity in PKAN. © 2005 Movement Disorder Society [source]


Genetic counseling and "molecular" prenatal diagnosis of holoprosencephaly (HPE),

AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010
Sandra Mercier
Abstract Holoprosencephaly (HPE) is a structural anomaly of the developing brain in which the forebrain fails to divide into two separate hemispheres and ventricles. The poor prognosis in the most severe forms justifies the importance of genetic counseling in affected families. The genetic counseling requires a thorough clinical approach given the extreme variability of phenotype and etiology. The karyotype is an essential diagnostic tool. Since mutations in the four major genes (SHH, ZIC2, SIX3, and TGIF) have been identified in HPE patients, molecular study is performed routinely in nonsyndromic HPE. New molecular tools, such as array-CGH analysis, are now part of the diagnostic process. Prenatal diagnosis is based primarily on fetal imaging, but "molecular" prenatal diagnosis can be performed if a mutation has been previously identified in a proband. Interpretations of molecular diagnosis must be given with caution, given the lack of strict genotype,phenotype correlation, and should be offered in addition to fetal imaging, using ultrasound followed by fetal MRI. We report on our experience of 15 molecular prenatal diagnoses from chorionic villi or amniotic fluid sampling. In eight instances, we were able to reassure the parents after taking into account the absence of the mutation in the fetus, previously identified before in a parent and/or a proband. Fetal RMI was normal later in pregnancy, and no child had medical problems after birth. The mutation was found in the seven other cases: four children were born, either without brain malformation and asymptomatic, or had a less severe form than the index case. © 2010 Wiley-Liss, Inc. [source]


Primary male infertility in Kuwait: a cytogenetic and molecular study of 289 infertile Kuwaiti patients

ANDROLOGIA, Issue 3 2007
F. Mohammed
Summary Infertility is one of the major public health problems, affecting 15% of couples who attempt pregnancy; in 50% of these, the male partner is responsible. Chromosomal abnormalities and Y microdeletions in the azoospermia factor (AZF) region are known to be associated with spermatogenetic failure. In the present study, 289 patients with primary male infertility because of spermatogenetic failure were studied in order to highlight the molecular background of male infertility in Kuwait, and to avoid the possibility of transmission of any microdeletions/chromosomal aberrations to offspring via intracytoplasmic sperm injection (ICSI). Of the 289 infertile men, 23 patients (8%) had chromosomal aberration in the form of Klinefelter syndrome/variant (16/23; 69.6%), XYY syndrome (3/23; 13%), XX male syndrome (2/23; 8.7%), 45,X/46X, i(Yp)(1/23; 4.4%) and 45,XY, t(9;22) (1/23;4.4%). Y-chromosome microdeletion in the AZFb and AZFc regions were detected in 7/266 cases (2.6%). Testicular biopsy was carried out in 31 azoospermic patients, of whom five men had Sertoli-cell only syndrome, while 26 patients had spermatogenic arrest. In conclusion, this study showed that the frequency of both chromosomal anomalies and Y microdeletions were found in 10.4% of the infertile men. The potential risk of transmitting these genetic disorders to offspring provides a rationale for screening infertile men prior to ICSI. [source]


A clinical, cytogenetic and molecular study of 47 females with r(X) chromosomes

ANNALS OF HUMAN GENETICS, Issue 4 2000
N. DENNIS
We studied 47 patients with a 45,X/46,X,r(X) karyotype to identify phenotypic differences between these patients and 45,X patients, and to determine whether these differences could be explained by the status of genes within the ring. Only 2 patients had the ,severe' r(X) phenotype, and both were consistent with this resulting from functional disomy of genes normally subject to X inactivation. A further 7 patients also carried active rings but these patients did not have a more severe phenotype than those whose rings were inactivated, probably because their rings were smaller and did not contain the (as yet unidentified) genes whose functional disomy is particularly damaging. Patients with a r(X) did not show clear physical differences when compared with a 45,X series, except for a possible reduction in the frequency of oedema in those whose r(X) had an Xq breakpoint distal to DXS128E, at Xq13.2. Thus some protection from oedema may be provided by the presence of two copies of Xq13.2. [source]


A clinical trial and molecular study of photoadaptation in vitiligo

BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2009
C.L. Hexsel
Summary Background, Photoadaptation to ultraviolet (UV) B phototherapy is due to both pigmentary and nonpigmentary influences. Objectives, To measure photoadaptation in vitiliginous skin and to compare it with normal pigmented skin. Methods, Seventeen patients with Fitzpatrick skin phototypes III,VI with vitiligo received six to nine UVB treatments, two to three times weekly. Minimal erythema dose (MED) testing was done at baseline and after all treatments; the percentage change in MED was analysed as a measure of photoadaptation. The percentage decrease in cyclobutane pyrimidine dimers (CPDs) over 24 h after a single exposure of 1 MED was analysed on vitiliginous and normal skin. Results, The mean ± SD percentage change in MED from before to after treatments was: treated vitiliginous skin 28·5 ± 39·9% (P = 0·015), treated normal skin 35·9 ± 49·9% (P = 0·015), untreated vitiliginous skin 11·9 ± 22·6% (P =0·070), untreated normal skin 25·1 ± 41·3% (P = 0·041). Of these patients, two-thirds had a positive percentage change in MED (photoadaptation). The mean amount of CPDs induced per megabase of DNA immediately after exposure was significantly higher in vitiliginous skin. The mean ± SD percentage decrease in CPDs (rate of repair) in 24 h was 35·7 ± 26·8% in vitiliginous skin (P = 0·027) and 46·2 ± 19·5% in normally pigmented skin (P = 0·001); no difference was noted in the repair in vitiliginous skin compared with normal skin (P = 0·4). Conclusions, Photoadaptation in vitiliginous and normal skin was observed in two-thirds of patients. Vitiliginous skin had significantly more CPDs following UVB exposure; the rate of repair of UVB-induced DNA damage was equivalent to that in normal skin. [source]


Correlative analysis of gene expression profile and prognosis in patients with gliomatosis cerebri

CANCER, Issue 16 2009
Oscar Fernando D'Urso PhD
Abstract BACKGROUND: In modern clinical neuro-oncology, the pathologic diagnoses are very challenging, creating significant clinical confusion and affecting therapeutic decisions and prognosis. METHODS: TP53 and PTEN gene sequences were analyzed, and microarray expression profiling was also performed. The authors investigated whether gene expression profiling, coupled with class prediction methodology, could be used to determine the prognosis of gliomatosis cerebri in a more consistent manner than standard pathology. RESULTS: The authors reported the results of a molecular study in 59 cases of gliomatosis cerebri, correlating these results with prognosis. The well-known prognostic factors of gliomas (ie, age, Karnofsky performance status, histology [grade 2 vs 3], and contrast enhancement) were found to be predictive of response or outcome in only a percentage of patients but not in all patients. The authors identified a 23-gene signature that was able to predict patient prognosis with microarray gene expression profiling. With the aim of producing a prognosis tool that is useful in clinical investigation, the authors studied the expression of this 23-gene signature by real-time quantitative polymerase chain reaction. Real-time expression values relative to these 23 gene features were used to build a prediction method able to distinguish patients with a good prognosis (those more likely to be responsive to therapy) from patients with a poor prognosis (those less likely to be responsive to therapy). CONCLUSIONS: The results of the current study demonstrated not only a strong association between gene expression patterns and patient survival, but also a robust replicability of these gene expression,based predictors. Cancer 2009. © 2009 American Cancer Society. [source]


Facioscapulohumeral muscular dystrophy: epidemiological and molecular study in a north-east Italian population sample

CLINICAL GENETICS, Issue 6 2009
ML Mostacciuolo
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease associated with a partial deletion on chromosome 4q35. Few relevant investigations have been reported on its epidemiology and were essentially based on clinical diagnosis, having been performed before recognition of the molecular mutation. We report an epidemiological survey on FSHD patients, in which the diagnosis was obtained by combined clinical and molecular evaluation. The survey concerned the north-east Italian province of Padova, an area of 871,190 inhabitants (1 January 2004). We identified 40 patients affected by FSHD based on clinical diagnosis. In 33 of them, the EcoRI fragment size in the 4q35 region ranged from 14 to 35 kb. Four other patients belonging to the same family harbored a 38-kb fragment. In these four cases, the relationship between the borderline deletion with the mild FSHD phenotype was corroborated by additional haplotype reconstruction and segregation analysis. Interestingly, the same mild facial-sparing clinical pattern was apparent only in one other patient with an EcoRI fragment of 32 kb, suggesting that this unusual FSHD phenotype may be due to very small 4q35 deletions. On the whole, estimating a prevalence rate of 44 × 10,6, our survey confirmed FSHD as one of the most frequent neuromuscular disorders in Western populations. [source]


Clinical and Molecular diagnosis of the skeletal dysplasias associated with mutations in the gene encoding Fibroblast Growth Factor Receptor 3 (FGFR3) in Portugal

CLINICAL GENETICS, Issue 2 2009
MR Almeida
Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) and Lacrimo-Auriculo-Dento-Digital Syndrome (MIM 149730). Here we report a clinical and molecular study in a large cohort of 125 Portuguese patients with these skeletal disorders. The identification of the P250R mutation allowed the confirmation of the Muenke Syndrome in 9 out of the 52 cases referred. Two known mutations were found in the Thanatophoric Dysplasia referred cases. No mutations were identified in the LADD syndrome patient. In Achondroplasia and Hypochondroplasia, genetic heterogeneity was present amongst the 70 clinically diagnosed patients with 5 different mutations identified. As in other studies, complex phenotypic heterogeneity amongst patients carrying the same gene defect was observed. In several cases, the new amino acids encoded, as a consequence of mutations, were related to the severity of patients' phenotype. The presence of 10 misdiagnosed cases emphasizes the importance of performing mutation analysis of the hotspot regions responsible for both dysplasias (Ach and Hch). For patients with an unquestionable clinical diagnosis, lacking the most common mutations, a complete screening of FGFR3 is necessary. [source]