ABSTRACT
OBJECTIVE: To study connexin 26 (Cx26) gene mutations among autosomal recessive non-syndromal hearing loss in Kuwaiti patients and evaluate their effect on phenotypes. SUBJECTS AND METHODS: This cross sectional study included 100 patients aged between 6 months and 18 years, who were referred to the Sheikh Salem Al-Ali Centre for audiology and speech evaluation of autosomal recessive non-syndromic sensorineural hearing loss confirmed by clinico-genetic evaluation and a battery of diagnostic tests. Gene profiling and sequencing were performed to detect the presence and nature of Cx26 mutation. RESULTS: Of the 100 patients, mutation of Cx26 gene was detected in 15 patients (15%) of which 9 (60%) cases were heterozygous and 6 cases (40%) were homozygous. Eighty per cent of the 15 Cx26 positive cases resulted from the 35delG mutation. Among the heterozygous cases, 6 (66.6%) were positive for 35delG. All 6 homozygous patients were positive for the 35delG mutation. A significant correlation was found between genetic findings (p = 0.013) and family history (p = 0.029), as well as the onset (p = 0.015), course (p = 0.033), degree and configuration of hearing loss (p = 0.001). CONCLUSION: Among the selected Kuwaiti population sample, the Cx26 gene mutation was responsible for 15% of autosomal recessive non-syndromic sensorineural hearing loss. We recommend that screening for Cx26 gene mutation be considered in the screening strategy of patients with non-syndromic childhood hearing loss for counselling and management purposes. .
Subject(s)
Connexins/genetics , Hearing Loss, Sensorineural/genetics , Child , Child, Preschool , Connexin 26 , Consanguinity , Cross-Sectional Studies , Female , Heterozygote , Humans , Infant , Male , Mutation , Polymerase Chain ReactionABSTRACT
Despite significant heritability of autism spectrum disorders (ASDs), their extreme genetic heterogeneity has proven challenging for gene discovery. Studies of primarily simplex families have implicated de novo copy number changes and point mutations, but are not optimally designed to identify inherited risk alleles. We apply whole-exome sequencing (WES) to ASD families enriched for inherited causes due to consanguinity and find familial ASD associated with biallelic mutations in disease genes (AMT, PEX7, SYNE1, VPS13B, PAH, and POMGNT1). At least some of these genes show biallelic mutations in nonconsanguineous families as well. These mutations are often only partially disabling or present atypically, with patients lacking diagnostic features of the Mendelian disorders with which these genes are classically associated. Our study shows the utility of WES for identifying specific genetic conditions not clinically suspected and the importance of partial loss of gene function in ASDs.
Subject(s)
Autistic Disorder/diagnosis , Autistic Disorder/genetics , Exome/genetics , Genome-Wide Association Study/methods , Adolescent , Animals , Cells, Cultured , Child , Child, Preschool , Cohort Studies , Female , Humans , Male , Pedigree , Rats , Sequence Analysis, DNA/methods , Young AdultABSTRACT
Screening of 1,080 Kuwaiti male blood donors for glucose-6-phosphate dehydrogenase (G6PD) deficiency revealed this condition in 70 (6.5%) individuals. Mutation analysis of all 70 G6PD deficient samples performed by PCR/RFLP and direct sequencing identified the 563C-->T (Mediterranean) in 72.9%, 202G-->A (A(-)) in 14.3%, 1003G-->A (Chatham) in 7.1%, and 143T-->C (Aures) in 1.4%. In 3 cases (4.3%) mutations remain unknown. Genotyping of all G6PD deficient samples for UDP-glucuronosyltransferase 1 (UDPGT1) gene promoter polymorphism revealed (ta)6/(ta)6 in 38.6%, (ta)7/(ta)7 in 15.7%, (ta)6/(ta)7 in 44.3%, and (ta)7/(ta)8 allele in 1.4% of cases. Thus, 4% of males in the Kuwaiti population have G6PD deficiency coexisting with low activity of the UDPGT1 promoter.
