The present study suggests that mutations in MYO7A and CDH23 are the two major components of causes for USH1, while PCDH15, USH1C, and SANS are less frequent causes.
Our study expands the mutational spectrum of MYO7A and provides a foundation for further investigations elucidating the MYO7A-related mechanisms of USH1.
The finding of a MYO7A mutation in two related Hutterite families from northern Alberta provides evidence of genetic heterogeneity in Hutterites affected by Usher syndrome type I.
Six mutations in MYO7A were found in five patients, including two novel mutations c.397C > G (His133Asp) and 1244-2A > G (Glu459Stop), accounting for 42% of our USH1 patients.
Molecular diagnosis in Usher syndrome type 1 and 2 patients led to the identification of 21 sequence variations located in noncanonical positions of splice sites in MYO7A, CDH23, USH1C, and USH2A genes.
Primers covering the complete myosin VIIA coding sequence as well as the 3' non coding sequence were designed, allowing direct sequence analysis of each of the 48 coding exons and flanking splice sites in seven patients affected by USH1.
Usher syndrome type I (US1) is an autosomal recessive condition in which three different genes have been already localised (USH1A, USH1B, and USH1C on chromosomes 14q32, 11q13, and 11p15 respectively).
Many disease-causative mutations have been identified in MYO7A and USH2A genes, which play a major role in Usher syndrome type I and type II, respectively.
In this study, 66 unrelated patients with USH1 were evaluated for defects in MYO7A using single-strand conformation polymorphism analysis and direct genomic sequencing.
In this study, we identified two novel mutations, c.3742G>A (p.E1248K) and c.6051+1G>A (donor splice site mutation in intron 44), of MYO7A in a Chinese non-consanguineous family with USH1.