Abstract
BackgroundUsher syndrome (USH) is an autosomal recessive disorder characterized by hearing impairment and vision dysfunction due to retinitis pigmentosa. Phenotypic and genetic heterogeneities of this disease make it impractical to obtain a genetic diagnosis by conventional Sanger sequencing.MethodsIn this study, we applied a next-generation sequencing approach to detect genetic abnormalities in patients with USH. Two unrelated Chinese families were recruited, consisting of two USH afflicted patients and four unaffected relatives. We selected 199 genes related to inherited retinal diseases as targets for deep exome sequencing. Through systematic data analysis using an established bioinformatics pipeline, all variants that passed filter criteria were validated by Sanger sequencing and co-segregation analysis.ResultsA homozygous frameshift mutation (c.4382delA, p.T1462Lfs*2) was revealed in exon20 of gene USH2A in the F1 family. Two compound heterozygous mutations, IVS47 + 1G > A and c.13156A > T (p.I4386F), located in intron 48 and exon 63 respectively, of USH2A, were identified as causative mutations for the F2 family. Of note, the missense mutation c.13156A > T has not been reported so far.ConclusionIn conclusion, targeted exome sequencing precisely and rapidly identified the genetic defects in two Chinese USH families and this technique can be applied as a routine examination for these disorders with significant clinical and genetic heterogeneity.
Highlights
Usher syndrome (USH) is an autosomal recessive disorder characterized by hearing impairment and vision dysfunction due to retinitis pigmentosa
USH is divided into clinical subtypes I, II, or III, based on severity and progression of vision and hearing loss [2]
Clinical diagnosis of Usher syndrome was based on examination of audiologic function, visual acuity, fundus photography and optical coherence tomography (OCT)
Summary
Usher syndrome (USH) is an autosomal recessive disorder characterized by hearing impairment and vision dysfunction due to retinitis pigmentosa. Usher syndrome (USH) is the most prevalent cause of hereditary deafness-blindness in humans [1]. It occurs in approximately 1 of 25,000 persons worldwide. Patients with Usher I have congenital deafness and begin to lose their vision early in life. They exhibit difficulty balancing due to vestibular problems. Patients with Usher II exhibit congenital hearing loss that is mild-moderate in low tones and moderate to severe at higher frequencies. They generally have a normal vestibular system.
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