title: Whole-exome sequencing revealed two novel mutations in Usher syndrome.
abstract: Usher syndrome is a clinically and genetically heterogeneous autosomal recessive inherited disorder accompanied by hearing loss and retinitis pigmentosa (RP). Since the associated genes are various and quite large, we utilized whole-exome sequencing (WES) as a diagnostic tool to identify the molecular basis of Usher syndrome. DNA from a 12-year-old male diagnosed with Usher syndrome was analyzed by WES. Mutations detected were confirmed by Sanger sequencing. The pathogenicity of these mutations was determined by in silico analysis. A maternally inherited deleterious frameshift mutation, c.14439_14454del in exon 66 and a paternally inherited non-sense c.10830G>A stop-gain SNV in exon 55 of USH2A were found as two novel compound heterozygous mutations. Both of these mutations disrupt the C terminal of USH2A protein. As a result, WES revealed two novel compound heterozygous mutations in a Turkish USH2A patient. This approach gave us an opportunity to have an appropriate diagnosis and provide genetic counseling to the family within a reasonable time.
authors.affiliation: Department of Medical Genetics, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
authors.forename: Asuman
authors.initials: A
authors.lastname: Koparir
authors.affiliation: Department of Medical Genetics, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey; Molecular Biology and Genetics Department, Erzurum Technical University, Erzurum, Turkey.
authors.forename: Omer Faruk
authors.initials: OF
authors.lastname: Karatas
authors.affiliation: American Hospital, Family Medicine Department, Istanbul, Turkey.
authors.forename: Ali Timucin
authors.initials: AT
authors.lastname: Atayoglu
authors.affiliation: Genetic Engineering and Biotechnology Institute, TUBITAK Marmara Research Center, Kocaeli, Turkey.
authors.forename: Bayram
authors.initials: B
authors.lastname: Yuksel
authors.affiliation: Advanced Genomics and Bioinformatics Research Center (İGBAM), BİLGEM, TUBITAK, Kocaeli, Turkey.
authors.forename: Mahmut Samil
authors.initials: MS
authors.lastname: Sagiroglu
authors.affiliation: Department of Medical Genetics, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Seven
authors.affiliation: Department of Medical Genetics, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Ulucan
authors.affiliation: Biruni University, Istanbul, Turkey.
authors.forename: Adnan
authors.initials: A
authors.lastname: Yuksel
authors.affiliation: Department of Medical Genetics, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey; Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USA; Biruni University, Istanbul, Turkey. Electronic address: mozen@bcm.edu.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ozen
mesh_terms: D002648:Child; D055106:Genome-Wide Association Study / Q000379:methods; D034381:Hearing Loss / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D012174:Retinitis Pigmentosa / Q000235:genetics; D052245:Usher Syndromes / Q000235:genetics*
keywords: USH2A; Usher syndrome; Whole exome sequencing