MYO7A mutation screening in Usher syndrome type I patients from diverse origins

Usher syndrome (USH) (OMIM 276901) is an autosomal recessive disorder characterised by hearing impairment associated with retinitis pigmentosa and in some cases vestibular dysfunction. This disease accounts for approximately 50% of individuals with combined deafness and blindness in developed countries. The estimated prevalence of USH ranges from 3.8 to 6.2/100 000.1–3 Phenotypically, three clinical types of Usher syndrome have been defined according to the severity of hearing impairment, age of retinitis pigmentosa onset and the presence or absence of vestibular response. Usher syndrome type I (USH1) is the most serious type, characterised by severe to profound congenital sensorineural hearing loss, balance deficiency and prepubertal onset of retinitis pigmentosa leading to blindness. USH2 is characterised by moderate to severe hearing impairment, normal vestibular function and later onset of retinal degeneration than USH1. USH3 displays progressive hearing loss, retinitis pigmentosa and variable vestibular phenotype. Six loci for USH1 (USH1B–USH1G) have been mapped and, to date, five genes have been identified.4,5 The MYO7A gene was found to be responsible for USH1B6 and is the most common subtype of USH1, accounting for approximately 50% of cases.7–9 Defects in MYO7A also cause autosomal dominant non-syndromic sensorineural hearing impairment (DFNA11) (MIM 601317),10 autosomal recessive deafness (DFNB2) (MIM 600060)11,12 as well as atypical types of Usher syndrome which are clinically similar to USH3.13 The MYO7A gene has 49 exons, of which 48 are coding, and spans approximately 87 kb of genomic sequence on chromosome 11q13.5. The encoded protein is an unconventional myosin, the myosin VIIA,14 predicted to consist of 2215 amino acids and has a molecular mass of 254 kDa. This protein contains three typical domains: the N terminal head or motor; the neck or regulatory domain consisting of five IQ motifs; and the tail …