CDH23 Mutation and Phenotype Heterogeneity: A Profile of 107 Diverse Families with Usher Syndrome and Nonsyndromic Deafness

摘要: Usher syndrome type I is characterized by congenital hearing loss, retinitis pigmentosa (RP), and variable vestibular areflexia. ID, one of seven genetic localizations, have been mapped to a chromosomal interval that overlaps with nonsyndromic-deafness localization, DFNB12. Mutations in CDH23, gene encodes putative cell-adhesion protein multiple cadherin-like domains, are responsible for both DFNB12 nonsyndromic deafness. Specific CDH23 mutational defects identified differentiate these two phenotypes. Only missense mutations observed families deafness, whereas nonsense, frameshift, splice-site, syndrome. In the present study, panel 69 probands 38 recessive deafness were screened presence entire coding region heteroduplex, single-strand conformation polymorphism, direct sequence analyses. A total 36 different detected 45 families; 33 novel, including 18 missense, 3 5 splicing defects, microdeletions, 2 insertions. common more than family. Numerous exonic intronic polymorphisms also detected. Results ophthalmologic examinations patients found asymptomatic RP-like manifestations, indicating may subtle effect retina. Furthermore, display wide range loss RP phenotypes, differing severity, age at onset, type, or absence