Original Investigation

Human Genetics

, Volume 116, Issue 4, pp 292-299

First online:

Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population

  • Xiao Mei OuyangAffiliated withDepartment of Otolaryngology (D-48), University of Miami
  • , Denise YanAffiliated withDepartment of Otolaryngology (D-48), University of Miami
  • , Li Lin DuAffiliated withDepartment of Otolaryngology (D-48), University of Miami
  • , J. Fielding. HejtmancikAffiliated withNational Eye Institute/NIH
  • , Samuel G. JacobsonAffiliated withScheie Eye Institute, University of Pennsylvania
  • , Walter E. NanceAffiliated withDepartment of Human Genetics, Virginia Commonwealth University
  • , An Ren LiAffiliated withNational Eye Institute/NIH
  • , Simon AngeliAffiliated withDepartment of Otolaryngology (D-48), University of Miami
  • , Muriel KaiserAffiliated withNational Eye Institute/NIH
    • , Valerie NewtonAffiliated withCenter for Audiology, University of Manchester
    • , Steve D. M. BrownAffiliated withMRC Mouse Genome Centre and MRC Mammalian Genetics Unit
    • , Thomas BalkanyAffiliated withDepartment of Otolaryngology (D-48), University of Miami
    • , Xue Zhong LiuAffiliated withDepartment of Otolaryngology (D-48), University of Miami Email author 

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Usher syndrome type I (USH1), the most severe form of this syndrome, is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. At least seven USH1 loci, USH1A-G, have been mapped to the chromosome regions 14q32, 11q13.5, 11p15, 10q21-q22, 21q21, 10q21-q22, and 17q24-25, respectively. Mutations in five genes, including MYO7A, USH1C, CDH23, PCDH15 and SANS, have been shown to be the cause of Usher syndrome type 1B, type 1C, type 1D, type 1F and type 1G, respectively. In the present study, we carried out a systematic mutation screening of these genes in USH1 patients from USA and from UK. We identified a total of 27 different mutations; of these, 19 are novel, including nine missense, two nonsense, four deletions, one insertion and three splicing defects. Approximatelly 35–39% of the observed mutations involved the USH1B and USH1D genes, followed by 11% for USH1F and 7% for USH1C in non-Acadian alleles and 7% for USH1G. Two of the 12 MYO7A mutations, R666X and IVS40-1G>T accounted for 38% of the mutations at that locus. A 193delC mutation accounted for 26% of CDH23 (USH1D) mutations, confirming its high frequency. The most common PCDH15 (USH1F) mutation in this study, 5601-5603delAAC, accounts for 33% of mutant alleles. Interestingly, a novel SANS mutation, W38X, was observed only in the USA cohort. 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.