Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis

Hum Mutat. 2001;17(1):34-41. doi: 10.1002/1098-1004(2001)17:1<34::AID-HUMU4>3.0.CO;2-O.


Usher syndrome (USH) is a clinically and genetically heterogeneous autosomal recessive disorder in which sensorineural hearing loss is associated with retinitis pigmentosa. Usher syndrome type 1, the most severe form, is characterized by profound congenital deafness, vestibular dysfunction, and prepubertal onset of retinitis pigmentosa. Six different USH1 genes have so far been mapped, of which two have already been identified. MYO7A, encoding the unconventional myosin VIIA, underlies USH1B. Recently, the USH1C gene was shown to encode harmonin, a PDZ domain-containing protein. A previous screening of 18 unrelated USH1 patients, without a detected MYO7A mutation, for the three USH1C mutations described to date had demonstrated the presence of the 238-239insC mutation in the heterozygous state in four of them. A complete USH1C mutation screening in these four carriers of the 238-239insC mutation resulted in the detection of the second mutation in all the individuals, and the identification of three novel mutations, namely two splice site mutations (IVS1+1G>T and IVS5+1G>A) and a nonsense mutation (R31X). Thirty-one polymorphisms were detected in the USH1C gene. We observed that the E519D substitution is non-pathogenic, which is of particular interest for molecular diagnosis. Our analysis indicated that all the carriers of the 238-239insC mutation share a common haplotype. A different common haplotype was found in the two IVS1+1G>T carriers. Future studies of additional carriers and non-carriers should document the here proposed founder effect of these two mutations.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Adaptor Proteins, Signal Transducing
  • Alternative Splicing / genetics
  • Amino Acid Substitution / genetics
  • Carrier Proteins / genetics
  • Child
  • Codon, Nonsense / genetics
  • DNA Mutational Analysis
  • Deafness / congenital
  • Deafness / genetics*
  • Female
  • Genetic Carrier Screening
  • Haplotypes / genetics*
  • Humans
  • Male
  • Mutation*
  • Mutation, Missense / genetics
  • Polymorphism, Genetic / genetics*
  • Retinitis Pigmentosa / congenital
  • Retinitis Pigmentosa / genetics*
  • Syndrome


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Codon, Nonsense
  • USH1C protein, human