Targeted exome sequencing identified a novel USH2A mutation in a Chinese Usher syndrome family: a case report
Abstract Background: Usher syndrome is a king of phenotypic and genetic heterogeneous disease. Our purpose was to identify the gene mutation in a Chinese family with Usher syndrome type 2 and describe the clinical features.Case presentation: A 23-year-old man complained of 10-year nyctalopia and a 3-year decline in visual acuity of both eyes accompanied by congenital dysaudia. To clarify the diagnosis, the clinical symptoms were observed and analysed in combination with comprehensive ophthalmologic examinations as well as genetic analysis (Targeted exome sequencing, TES). Typical clinical presentation of Usher syndrome on fundus was found including a wax yellow-like disc, bone-spicule formations and retinal vessel stenosis. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) showed the loss of ellipsoid zone and the reduction in paracaval vessel density of both eyes. Genetic analysis identified a novel homozygote of c.8483_8486del (p.Ser2828*) in USH2A. The mutation of premature translation termination causes the deletion of 19 fibronectin type 3 domains(FN3), transmembrane region (TM) and PDZ-binding motif domain, which plays an important role in protein binding. Combining the clinical manifestation and genetic result, the patient was diagnosed with Usher syndrome type 2.Conclusions: We found a novel mutation of c.8483_8486del in USH2A gene through TES techniques. The result broaden the spectrum of mutations in Usher syndrome type 2 and suggest that the combination of clinical information and TES molecular diagnosis could help USH patients obtain a better diagnosis.