RT Journal Article
A1 Khalaileh, Ayat
A1 Abu-Diab, Alaa
A1 Ben-Yosef, Tamar
A1 Raas-Rothschild, Annick
A1 Lerer, Israela
A1 Alswaiti, Yahya
A1 Chowers, Itay
A1 Banin, Eyal
A1 Sharon, Dror
A1 Khateb, Samer
T1 The Genetics of Usher Syndrome in the Israeli and Palestinian Populations
JF Investigative Ophthalmology & Visual Science
JO Invest. Ophthalmol. Vis. Sci.
YR 2018
DO 10.1167/iovs.17-22817
VO 59
IS 2
SP 1095
OP 1104
SN 1552-5783
AB    Usher syndrome (USH) is the most common cause for deaf-blindness. It is genetically and clinically heterogeneous and prevalent in populations with high consanguinity rate. We aim to characterize the set of genes and mutations that cause USH in the Israeli and Palestinian populations.    Seventy-four families with USH were recruited (23 with USH type 1 [USH1], 33 with USH2, seven with USH3, four with atypical USH, and seven families with an undetermined USH type). All affected subjects underwent a full ocular evaluation. A comprehensive genetic analysis, including Sanger sequencing for the detection of founder mutations, homozygosity mapping, and whole exome sequencing in large families was performed.    In 79% of the families (59 out of 74), an autosomal recessive inheritance pattern could be determined. Mutation detection analysis led to the identification of biallelic causative mutations in 51 (69%) of the families, including 21 families with mutations in USH2A, 17 in MYO7A, and seven in CLRN1. Our analysis revealed 28 mutations, 11 of which are novel (including c.802G>A, c.8558+1G>T, c.10211del, and c.14023A>T in USH2A; c.285+2T>G, c.2187+1G>T, c.3892G>A, c.5069_5070insC, c.5101C>T, and c.6196C>T in MYO7A; and c.15494del in GPR98).    We report here novel homozygous mutations in various genes causing USH, extending the spectrum of causative mutations. We also prove combined sequencing techniques as useful tools to identify novel disease-causing mutations. To the best of our knowledge, this is the largest report of a genetic analysis of Israeli and Palestinian families (n = 74) with different USH subtypes.  
RD 3/5/2021
UL https://doi.org/10.1167/iovs.17-22817