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Samer Khateb, Ayat Khalaileh, Tamar Ben-Yosef, Annick Raas-Rothschild, Itay Chowers, Eyal Banin, Dror Sharon; The Genetics of Usher Syndrome in the Israeli and Palestinian Populations. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3154.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize the set of mutations and genes causing Usher syndrome (USH) in the Israeli and Palestinian populations
All participants in the study signed an informed consent that adhered to the tenets of the declaration of Helsinki before drawing a blood sample. Patients underwent clinical examination including electroretinography and retinal imaging. Genetic analysis included Sanger sequencing for the detection of founder mutations, homozygosity mapping in some consanguineous families, and whole exome sequencing (WES) in large families
Our cohort contains more than 1400 families with inherited retinal diseases, 83 of the index cases were diagnosed with Usher syndrome (26 with USH type 1 (USH1), 32 with USH2, 9 with USH3, one with atypical USH, and in 15 families the type could not be determined). In 55 of the families (~67%), the inheritance pattern was determined as autosomal recessive (AR) and the remaining were isolate cases. A comprehensive mutation detection analysis (including homozygosity mapping, screening for founder mutations and WES analysis in 8 cases) lead to the identification of the cause of disease in 31 (37%) of the families: (13 families with USH2A mutations, 9 MYO7A, 7 USH3A, 1 GPR98 and 1 CEP250). In an Ashkenazi Jewish family with USH3 (MOL1021), we identified a novel nonsense mutation (p.Tyr1768*) in the USH3A gene that is in a compound heterozygous state with the known founder mutation (p.N48K). In Muslim families from the vicinity of Jerusalem (MOL1019, MOL1191, MOL406), we identified two novel founder MYO7A mutations: p.G1298R and c.2187+1G>T (IVS18+1G>T). Finally, we report here of the first GPR98 mutation in the Israeli population: a homozygous frameshift mutation (p.K5l65fs) identified by WES analysis
The cause of disease in most USH families is still unknown and further analyses are needed to identify mainly family-specific mutations. Our data support previous studies indicating that MYO7A is the major USH1 gene, USH2A is the major USH2 gene, and USH3A the major USH3 gene
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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