Phenotype determination guides swift genotyping of a DFNA2/KCNQ4 family with a hot spot mutation (W276S).

Contains fulltext : 49141.pdf (publisher's version ) (Closed access)OBJECTIVE: Genotype a family trait with autosomal dominant nonsyndromic sensorineural hearing impairment guided only by the phenotype. STUDY DESIGN: Family study. SETTING: Tertiary referral center. PATIENTS: Fifteen family members. METHODS: In the first phase, sequence analysis was performed on DNA isolated from buccal swabs of the proband and her daughter, guided by the phenotype based on audiometric data that were already available. After detection of the W276S missense mutation in the KCNQ4 gene in both patients, this finding was confirmed in the other affected family members. All participants completed a questionnaire, were clinically examined, and underwent standard pure-tone audiometry. The results were analyzed to refine the phenotypic features of the family trait. RESULTS: All clinically affected participants were carriers of the W276S hotspot mutation in exon 5 of the KCNQ4 gene on chromosome 1p34. Refined phenotypic features confirmed previously described phenotypes of DFNA2 families. CONCLUSIONS: Phenotype determination can be cost saving and very effective in detecting the genotype of autosomal dominant nonsyndromic hearing impairment, especially when phenotype analyses can be performed on data that are already available or easily collected