title: Analysis of two Arab families reveals additional support for a DFNB2 nonsyndromic phenotype of MYO7A.
abstract: Variants in the head and tail domains of the MYO7A gene, encoding myosin VIIA, cause Usher syndrome type 1B (USH1B) and nonsyndromic deafness (DFNB2, DFNA11). In order to identify the genetic defect(s) underling profound deafness in two consanguineous Arab families living in UAE, we have sequenced a panel of 19 genes involved in Usher syndrome and nonsyndromic deafness in the index cases of the two families. This analysis revealed a novel homozygous insertion of AG (c.1952_1953insAG/p.C652fsX11) in exon 17 of the MYO7A gene in an Iraqi family, and a homozygous point mutation (c.5660C>T/p.P1887L) in exon 41 affecting the same gene in a large Palestinian family. Moreover, some individuals from the Palestinian family also harbored a novel heterozygous truncating variant (c.1267C>T/p.R423X) in the DFNB31 gene, which is involved in autosomal recessive nonsyndromic deafness type DFNB31 and Usher syndrome type II. Assuming an autosomal recessive mode of inheritance in the two inbred families, we conclude that the homozygous variants in the MYO7A gene are the disease-causing mutations in these families. Furthermore, given the absence of retinal disease in all affected patients examined, particularly a 28 year old patient, suggests that at least one family may segregate a DFNB2 presentation rather than USH1B. This finding further supports the premise that the MYO7A gene is responsible for two distinct diseases and gives evidence that the p.P1887L mutation in a homozygous state may be responsible for nonsyndromic hearing loss.
authors.affiliation: Department of Pathology, College of Medicine and Heath Sciences, United Arab Emirates University, Al Ain, United Arab Emirates, salmabs@uaeu.ac.ae.
authors.forename: Salma
authors.initials: S
authors.lastname: Ben-Salem
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Rehm
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Willems
authors.forename: Zakaria A
authors.initials: ZA
authors.lastname: Tamimi
authors.forename: Hammadi
authors.initials: H
authors.lastname: Ayadi
authors.forename: Bassam R
authors.initials: BR
authors.lastname: Ali
authors.forename: Lihadh
authors.initials: L
authors.lastname: Al-Gazali
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D016254:Mutagenesis, Insertional; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D014479:United Arab Emirates
chemical_list: C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009218:Myosins