Two truncating USH3A mutations, including one novel,in a German family with Usher syndrome

[摘要] Purpose: To identify the genetic defect in a German familywith Usher syndrome (USH) and linkage to the USH3A locus.Methods: DNA samples of five family members (both parents andthe three patients) were genotyped with polymorphic microsatellitemarkers specific for eight USH genes. Three affected family membersunderwent detailed ocular and audiologic characterization.Results: Symptoms in the patients were compatible with Ushersyndrome and show intrafamilial variation, for both hearing loss(ranging from severe to profound with non-linear progression) andvision. Genotyping of microsatellite markers for the different USH lociwas in line with a defect in the USH3A gene on chromosome 3q25.Sequence analysis of the USH3A gene revealed two truncatingmutations; c.149_152delCAGGinsTGTCCAAT, which has been describedpreviously, and a novel mutation, c.502_503insA, segregating with thephenotype.Conclusions: To date, only 11 USH3A mutations have beendescribed. This is the first description of a German family with USH dueto USH3A mutations, including one novel. Our findings indicate thatalso in the Central European population, USH3A mutations should beconsidered in cases of USH.

[学科分类] 生物化学/生物物理