Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness

Xiao Mei Ouyang, Xia Juan Xia, Elisabeth Verpy, Li Lin Du, Arti Pandya, Christine Petit, Thomas Balkany, Walter E. Nance, Xue Z Liu

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

We have recently shown that USH1C underlies Usher syndrome type 1c (USH1C), an USH1 subtype characterized by profound deafness, retinitis pigmentosa, and vestibular dysfunction. USH1C encodes a PDZ-domain-containing protein, harmonin. Eight different Ush1c transcripts were identified in the mouse inner ear. Moreover, trancsripts containing seven alternatively spliced exons (A-F, G/G) were found to be expressed in the inner ear, but not in the eye. These findings suggested that mutations involving USH1C might also be the cause of DFNB18, a form of non-syndromic deafness, which maps to a chromosomal region that includes USH1C. We screened 32 Chinese multiplex families with non-syndromic recessive deafness for USH1C mutations. In one family, congenital profound deafness without RP was associated with a C to G transversion in the alternatively spliced exon D, predicting an arginine to proline substitution at codon 608 in the proline-, serine- and threonine-rich region of harmonin. We also screened 320 deaf probands from other ethnic background and found three who were heterozygous for changes in the alternately spliced exons including Gly431 Val in exon B, Arg620Leu and Arg636Cys in exon D. None of these mutations were detected in DNA from 200 control subjects with normal hearing including 110 Chinese. We also screened 121 non-Acadian probands with type 1 Usher syndrome. Non carried any mutations in these exons of USH1C. Our findings show that USH1C mutations can also cause non-syndromic deafness and that some harmonin isoforms are specifically required for inner ear function.

Original languageEnglish
Pages (from-to)26-30
Number of pages5
JournalHuman Genetics
Volume111
Issue number1
DOIs
StatePublished - Jul 1 2002

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Deafness
Exons
Mutation
Inner Ear
Proline
Usher Syndromes
PDZ Domains
Retinitis Pigmentosa
Type 1C Usher syndrome
Threonine
Codon
Serine
Hearing
Arginine
Protein Isoforms
DNA

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness. / Ouyang, Xiao Mei; Xia, Xia Juan; Verpy, Elisabeth; Du, Li Lin; Pandya, Arti; Petit, Christine; Balkany, Thomas; Nance, Walter E.; Liu, Xue Z.

In: Human Genetics, Vol. 111, No. 1, 01.07.2002, p. 26-30.

Research output: Contribution to journalArticle

Ouyang, XM, Xia, XJ, Verpy, E, Du, LL, Pandya, A, Petit, C, Balkany, T, Nance, WE & Liu, XZ 2002, 'Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness', Human Genetics, vol. 111, no. 1, pp. 26-30. https://doi.org/10.1007/s00439-002-0736-0
Ouyang, Xiao Mei ; Xia, Xia Juan ; Verpy, Elisabeth ; Du, Li Lin ; Pandya, Arti ; Petit, Christine ; Balkany, Thomas ; Nance, Walter E. ; Liu, Xue Z. / Mutations in the alternatively spliced exons of USH1C cause non-syndromic recessive deafness. In: Human Genetics. 2002 ; Vol. 111, No. 1. pp. 26-30.
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