The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene

Nat Genet. 1997 Jun;16(2):191-3. doi: 10.1038/ng0697-191.

Abstract

Hereditary non-syndromic profound deafness affects about 1 in 2000 children prior to language acquisition. In 80% of the cases, the mode of transmission is autosomal recessive. The number of genes involved in these recessive forms of isolated deafness (DFNB genes) has been estimated to between 30 and 100. So far, ten DFNB genes have been mapped to human chromosomes, one of which has been isolated. By linkage analysis of a single family whose members were affected with profound deafness, some of them presenting with vestibular dysfunction, DFNB2 has been mapped to chromosome 11q13 (ref. 3). The gene responsible for a form of Usher syndrome type I, USH1B, has been assigned to the same chromosomal region. Usher syndrome associates profound congenital deafness and vestibular dysfunction with retinitis pigmentosa. In the homologous murine region are located the shaker-1 mutations responsible for deafness and vestibular dysfunction. It has been demonstrated that the murine shaker-1 and human USH1B phenotypes result from mutations in the gene encoding myosin-VIIA. Based on mapping data as well as on the similarities between the phenotypes of DFNB2-affected patients and shaker-1 mouse mutants, we have proposed that a defective myosin-VIIA may also be responsible for DFNB2 (ref. 1). Sequence analysis of each of the coding exons of the myosin-VIIA gene (MYO7A) was thus undertaken in the DFNB2-affected family. In the last nucleotide of exon 15, a G to A transition was detected, a type of mutation that is known to decrease the efficiency of splicing. Accordingly, this result shows that different mutations in MYO7A result in either an isolated or a syndromic form of deafness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Deafness / genetics*
  • Dyneins
  • Genes, Recessive*
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Myosin VIIa
  • Myosins / genetics*
  • Sequence Homology, Amino Acid
  • Syndrome

Substances

  • MYO7A protein, human
  • Myo7a protein, mouse
  • Myosin VIIa
  • Myosins
  • Dyneins

Associated data

  • GENBANK/A53016
  • GENBANK/J02974
  • GENBANK/L19401
  • GENBANK/U34227
  • GENBANK/U39226
  • GENBANK/U49739
  • GENBANK/U57053
  • GENBANK/X58479
  • GENBANK/X68199
  • GENBANK/X71997
  • GENBANK/X74800
  • GENBANK/X74815
  • GENBANK/X77609
  • GENBANK/X98411
  • GENBANK/X98507