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Affected Males (affected + male)
Selected AbstractsHomozygous feature of isolated triphalangeal thumb,preaxial polydactyly linked to 7q36: no phenotypic difference between homozygotes and heterozygotesCLINICAL GENETICS, Issue 1 2009CN Semerci Preaxial polydactyly is a common limb malformation in humans with variable clinical expression. Different types of triphalangeal thumb-preaxial polydactyly phenotypes were mapped to the chromosome 7q36 region. We studied a large Turkish family of 69 individuals, of whom 22 individuals were affected. In all, 11 affected family members were clinically and radiologically evaluated. All affected individuals had a triphalangeal thumb and a preaxial (hypoplastic) extra digit bilaterally, with minimal intrafamilial variation. No feet involvement was observed. Linkage and haplotype analyses using 20 informative meioses confirmed the 7q36 region contained the LIMBR1 gene. Maximum logarithm of the odds (LOD) scores were obtained with DNA markers D7S550 and D7S2423. We have further identified a novel C to T alteration at position 4909 bp in the critical zone of polarizing activity regulatory sequence (ZRS) region, in the intron 5, of the LMBR1 gene. One affected male with homozygous status and no phenotypic difference from affected family members with heterozygous status represented the first homozygote case of the triphalangeal thumb-preaxial polydactyly phenotype. [source] Evaluating the accuracy of Malformations Surveillance Program in detecting virilization due to congenital adrenal hyperplasiaCONGENITAL ANOMALIES, Issue 1 2005Julie Travitz ABSTRACT Malformations surveillance programs of newborn infants have been developed as a method for identifying serious and relatively common birth defects. The virilization of newborn infants with the classic 21-hydroxylase form of congenital adrenal hyperplasia must be identified early if the associated metabolic crisis in the perinatal period is to be prevented. We compared the detection of virilization associated with 21-hydroxylase congenital adrenal hyperplasia in infants by three methods: an ,active' malformations surveillance of medical records at a large urban hospital; routine medical care by examining physicians; and newborn biochemical screening of blood samples. The experience at a large maternity center in Boston, since 1972, showed that pediatricians often recognized affected females (6/6), but not males (0/2); the state newborn screening program, begun in 1990, identified correctly all affected males and females. The Active Malformations Surveillance Program was the least effective screening method, identifying four of six affected females and neither of the affected males. The low rate of detecting affected females by the Surveillance Program was attributed to a failure to sensitize the research assistants to the importance of physicians' notations regarding the signs and symptoms of virilization. The failure of examining physicians, and thereby, the malformations surveillance program, to detect virilized newborn males was due to the lack of consistent associated physical features. These comparisons between these three methods of detection can be used to design and improve malformations surveillance programs. [source] Prevalence and handedness correlates of traumatic injuries to the permanent incisors in 13,17-year-old adolescents in Erzurum, TurkeyDENTAL TRAUMATOLOGY, Issue 5 2003Varol Canakci Abstract ,,,The objectives of the present study were to explore the relationship between dental trauma and handedness, and to assess the prevalence of traumatic injuries to the permanent incisors of 13,17-year-old patients, seeking treatment for various dental conditions in Erzurum, Turkey. A questionnaire focusing on handedness was administered to these patients. Handedness was assessed by the Edinburgh Handedness Inventory (Oldfield, 1971). Hand preference was divided into two classes for convenience in data analysis: (i) right-handers (GSc from 80 to 100); and (ii) left-handers (GSc from ,80 to ,100). This study included the 13,17-year-old group patients who had GSc as described above. Thus, the present study was carried out on 2180 (1252 male and 928 female, with a mean age of 14.9 years) out of 2392 patients. The clinical examinations and radiographic assessments were performed in full-designed dental chairs. Preliminary analysis showed no differences in rates of handedness with respect to sex and age. Overall, 10.4% of the patients were left-handers. A total of 292 (13.4%) of 2180 patients examined had one or more traumatized permanent incisors. The proportion of dental trauma was significantly higher in males than in females, 17.41% in males as compared to 7.97% in females; and ratio of the affected males to females was about 2.18. Sex difference in the prevalence of traumatized permanent incisors was statistically significant (P < 0.001). That is, males had a significantly higher risk of dental trauma than females (P < 0.001; odds ratio: 2.49; 95% confidence interval (CI) 1.88, 3.23). There was a higher level of traumatized permanent incisors among left-handers than among right-handers. 28.3% of left-handers and 11.7% of right-handers had dental trauma. This difference in the prevalence of traumatized permanent incisors for handedness was statistically significant (P < 0.001). Indeed, left-handers had a significantly higher risk on dental trauma than right-handers (P < 0.001; odds ratio: 3.09; 95% CI 2.23, 4.29). The primary causative factor in the occurrence of trauma was the fall (27.7%). Then came violence and fight as the second most frequent cause of trauma (24%), followed by sports injury (18.8%). Trauma resulting from collisions and traffic accidents were accounted as 13.7 and 11.3% of all cases, respectively. The other causes were 4.5%. In conclusion, the present study suggests that left-handed adolescents have more frequent permanent incisor tooth trauma than right-handed adolescents. Left-handedness, therefore, appears to be a risk factor for trauma in 13,17-year-old adolescents. [source] The expanding clinical spectrum of Anderson,Fabry disease: a challenge to diagnosis in the novel era of enzyme replacement therapyJOURNAL OF INTERNAL MEDICINE, Issue 6 2004A. C. Hauser Abstract. Anderson,Fabry disease is an X-linked recessive lysosomal storage disease resulting from deficient ,-galactosidase A activity. The conception of the disease has changed within the last decade. Studies of the last years have shown that the disease is not limited to the classical full-blown manifestation in affected males, which is well known since more than a century, but may also occur in carrier females. The phenomenology may differ in severity and kind of organ manifestation. Cardiac and renal variants with solely disease manifestation of these organs have also been described in an increasing number. It is likely that a spectrum exists regarding ,-galactosidase A activity in both genders on the one hand, and an additional one regarding the severity and the number of organs affected on the other. The purpose of this review is to sharpen physicians' perception of this disease. Early and accurate diagnosis is mandatory considering that this disorder is now, after introduction of the novel enzyme replacement therapy, a treatable disease. [source] CMTX: heterozygosity for a GJB1/CX32 mutation in a XXY male results in a mild phenotypeJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004M Milani Mutations in the GJB1/Cx32 gene (Xq13.1) cause the most common X-linked form of CMT (CMTX1) and are the most frequent cause of CMT disease after the CMT1A duplication. The disorder is characterized by a moderate-to-severe neuropathy in affected males and mild-to-no symptoms in carrier females. We report here a CMT1A-negative family in which 4 females and 2 males were affected, exhibiting different disease severity. Molecular analysis of the GJB1/Cx32 gene uncovered a nonsense mutation (Arg22stop) in exon 2. The mutation, which had been previously described by others and observed by us in numerous other families, occurred in heterozygous form in the 4 females. However, while one of the two male patients was severely affected and shown to be hemizygous, as expected, the other was mildly affected and found to carry the mutation in heterozygous form. Genotyping at the SRY (Yp11.3) and DMD (Xp21) loci suggested the occurrence of the XXY genotype associated with Klinefelter syndrome. Microsatellite analysis indicated that the nondysjunctional error was of paternal origin, as it is usually observed in about half the cases. The patient had no children. At clinical examination, he exhibited a very mild neurologic phenotype and showed signs of hypogonadism (mild gynecomastia and small testes) as well as moderate cognitive impairment. Electrophysiologic, cytogenetic and endocrinologic investigations are in progress in order to define the unusual phenotype in this patient. [source] Health-related quality of life in a cohort of adult patients with mild hemophilia AJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2008M. WALSH Summary.,Objectives:,To compare the health-related quality of life among adult males affected with mild hemophilia A due to the same mutation (Val2016ala) to that of unaffected age and sex matched controls from the same general population. Methods:,The Short-Form 36 (SF-36) and Health Assessment Questionnaire (HAQ) were used to measure health-related quality of life and physical function. Other measures included bleeding history, a measure of joint damage, body mass index, age, and viral infection status. Cross-sectional data were collected through research clinics and a retrospective chart audit over a two-year period. Results and Conclusions:,The study included 47 affected males and 33 controls. The affected males had a higher level of co-morbidity, prior bleeding, and existing joint damage than controls. With the exception of the social function and health transition scales, mean scores for each of the SF-36 domains were worse among affected males. Mean differences were more than a clinically important five points in five of eight domains, with the general health scale showing more than a 10-point difference. Despite the degree of difference noted, only two of the differences were statistically significant (general health and role emotional scales) because of the small sample size and considerable individual variation in SF-36 scale scores. Multiple regression analyses suggested existing joint damage and presence of heart disease as the strongest associates of lower physical health-related quality of life. Joint damage in turn was partly related to prior hemarthroses. Compared to the Canadian population, affected males had lower scores in six out of eight SF-36 domains as well as the physical component summary score. There were no significant differences found in the HAQ scores between the two groups. So-called mild hemophilia A was associated with a negative effect on physical health-related quality of life, contributed to by joint damage as a result of prior bleeding. [source] Cosegregation of a Factor VIII Microsatellite Marker with Mild Hemophilia A in Golden Retriever DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2005Marjory B. Brooks Mild hemophilia A (factor VIII deficiency) was diagnosed in Golden Retrievers and pedigree studies were undertaken to test the cosegregation of an intragenic factor VIII marker with the disease phenotype. The study population consisted of 30 client-owned dogs (22 males and 8 females). Hemophilic males (n = 12) typically demonstrated prolonged bleeding after trauma or surgery rather than spontaneous hemorrhagic events. The affected males had a proportionate reduction in factor VIII coagulant activity (mean FVIII:C = 4%) and factor VIII protein concentration (mean FVIII:Ag = 3%). Twenty-five dogs (10 affected males, 8 clear males, 2 obligate carrier dams, and 5 suspect carrier daughters) were genotyped for a factor VIII microsatellite marker, with allele size assigned by an automated capillary electrophoresis system. Five distinct marker alleles were present in the study pedigree and a 300-base pair allele was found to segregate with the hemophilia A phenotype. The inheritance of the hemophilia-associated allele defined carrier status for 5 suspect daughters of obligate carrier dams. The limitations inherent to linkage analyses (ie, lack of access to key family members and homozygosity at the marker locus) did not preclude carrier detection in this pedigree. We conclude that genotype analysis for the intragenic factor VIII marker can aid in control of canine hemophilia A through enhanced carrier detection. [source] Anthropometric and cephalometric measurements in X-linked hypohidrotic ectodermal dysplasiaORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 4 2007MO Lexner Structured Abstract Authors,,, Lexner MO, Bardow A, Bjorn-Jorgensen J, Hertz JM, Almer L, Kreiborg S. Objective,,, To describe the somatic development and craniofacial morphology in males affected with hypohidrotic ectodermal dysplasia (HED) and female carriers and to find clinical markers for early clinical diagnosis of possible female carriers. Design,,, A clinical and radiographic examination of the affected males and the female carriers. Setting and sample population,,, Twenty-four affected males and 43 female carriers with a known mutation in the ED1 gene were examined in a dental clinic in either Copenhagen or Aarhus, Denmark. Experimental variables,,, Height, body mass index (BMI) and head circumference. Cephalometric analysis of the craniofacial morphology. Outcome measure,,, Data on the somatic and craniofacial development in the affected males and female carriers. Results,,, No difference was observed regarding body height in the affected males and female carriers, BMI values were lower than the mean in most affected boys and adolescence and head circumference was somewhat decreased in both groups compared to normative data. The cephalometric analysis showed a reduced maxilla length and prognathism, a normal size and shape of the mandible and a reduced sagittal jaw relationship in both HED groups. Furthermore, affected males had a retroclined nasal bone and a more anteriorly inclined maxilla. A short nose, protruding lips, reduced facial convexity and facial height, characterized the soft tissue profile of the affected males. In female carriers, the lips were significantly retruded when compared with controls. Conclusion,,, No specific somatic or cephalometric markers could be observed, in the female carrier group. [source] Gene expression profiling differentiates autism case,controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autismAUTISM RESEARCH, Issue 2 2009Valerie W. Hu Abstract Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests. The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders. DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into three phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls. Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity. Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups. Among the findings unique to the most severely affected ASD group are 15 genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism. Among the genes common to all three subgroups of ASD are 20 novel genes mostly in putative noncoding regions, which appear to associate with androgen sensitivity and which may underlie the strong 4:1 bias toward affected males. [source] 2466: Blue cone nonochromacy gene mutation in Asia: phenotype variabilityACTA OPHTHALMOLOGICA, Issue 2010P BITOUN Purpose A far East asian family with 4 affected maternal cousin males with congenital nystagmus, low vision and dyschromatopsia was investigated for a genetic cause after informed consent. Blue cone monochromacy is a rare form of X-linked visual handicap with dyschromatopsia. Methods Family members had ophthalmologic examination including visual acuity, fundoscopy , slit lamp, biomicroscopy,colour vision testing and ERG and VEP recordings.DNA analysis of the composition of the cone ospin gene cluster was performed by PCR and PCR/RFLP as well as direct sequencing of LWS opsin gene. Results A novel nonsense Mutation in the single Long wave sensitive opsin gene was identified in all affected males and carrier females. The variability of the phenotype as well as the added role of parental myopia transmission in the phenotype will be discussed. Conclusion This is the first reported molecular diagnosis of blue cone monochromacy in the Asian population. The compound effect of dominantly inherited myopia offers insight of the effect of the added mutational load in these patients. [source] Identification of a novel deletion in the OA1 gene: report of the first Spanish family with X-linked ocular albinismCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 5 2010Monica Martinez-Garcia PhD Abstract Background:, This study was undertaken to analyse the OA1 gene (GPR143) and its involvement in a Spanish family presenting with nystagmus, a common symptom of X-linked ocular albinism (XLOA). Methods:, DNA samples from the index case and eight relatives were analysed by multiplex ligation-dependent probe amplification (MLPA). Sequence analysis and restriction assay were used to confirm the results. In addition, an analysis of a STR located in intron 1 of the OA1 gene (OA-CA) was performed. Results:, The father of the proband presented with nystagmus, a feature consistent with XLOA. Mutation screening by multiplex ligation-dependent probe amplification and sequence analysis of the exon 2 of the OA1 gene led to the identification of the novel p.Glu129fsX35 (g.5815delA) mutation in two affected males and four carrier females. Three relatives were found to be non-mutated. The deletion detected resulted in a truncated protein 35 codons downstream and generated a new restriction site for the XcmI endonuclease. Additionally, microsatellite analysis showed co-segregation with the disease in the family. Conclusions:, A novel deletion in the OA1 gene was identified in a Spanish family with ocular albinism. The mutation detected is likely a loss-of-function alteration. To the best of our knowledge, we describe the first Spanish family known to present with XLOA due to mutations in the OA1 gene. [source] The clinical picture of the Börjeson,Forssman,Lehmann syndrome in males and heterozygous females with PHF6 mutationsCLINICAL GENETICS, Issue 3 2004G Turner The usual description of the Börjeson,Forssman,Lehmann syndrome (BFLS) is that of a rare, X-linked, partially dominant condition with severe intellectual disability, epilepsy, microcephaly, coarse facial features, long ears, short stature, obesity, gynecomastia, tapering fingers, and shortened toes. Recently, mutations have been identified in the PHF6 gene in nine families with this syndrome. The clinical history and physical findings in the affected males reveal that the phenotype is milder and more variable than previously described and evolves with age. Generally, in the first year, the babies are floppy, with failure to thrive, big ears, and small external genitalia. As schoolboys, the picture is one of learning problems, moderate short stature, with emerging truncal obesity and gynecomastia. Head circumferences are usually normal, and macrocephaly may be seen. Big ears and small genitalia remain. The toes are short and fingers tapered and malleable. In late adolescence and adult life, the classically described heavy facial appearance emerges. Some heterozygous females show milder clinical features such as tapering fingers and shortened toes. Twenty percent have significant learning problems, and 95% have skewed X inactivation. We conclude that this syndrome may be underdiagnosed in males in their early years and missed altogether in isolated heterozygous females. [source] | |||||||||||||