Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3

Am J Hum Genet. 2001 Oct;69(4):673-84. doi: 10.1086/323610. Epub 2001 Aug 27.


Usher syndrome type 3 (USH3) is an autosomal recessive disorder characterized by progressive hearing loss, severe retinal degeneration, and variably present vestibular dysfunction, assigned to 3q21-q25. Here, we report on the positional cloning of the USH3 gene. By haplotype and linkage-disequilibrium analyses in Finnish carriers of a putative founder mutation, the critical region was narrowed to 250 kb, of which we sequenced, assembled, and annotated 207 kb. Two novel genes-NOPAR and UCRP-and one previously identified gene-H963-were excluded as USH3, on the basis of mutational analysis. USH3, the candidate gene that we identified, encodes a 120-amino-acid protein. Fifty-two Finnish patients were homozygous for a termination mutation, Y100X; patients in two Finnish families were compound heterozygous for Y100X and for a missense mutation, M44K, whereas patients in an Italian family were homozygous for a 3-bp deletion leading to an amino acid deletion and substitution. USH3 has two predicted transmembrane domains, and it shows no homology to known genes. As revealed by northern blotting and reverse-transcriptase PCR, it is expressed in many tissues, including the retina.

Publication types

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

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Base Sequence
  • Chromosomes, Human, Pair 3 / genetics*
  • Cloning, Molecular
  • Contig Mapping
  • Deafness / genetics*
  • Expressed Sequence Tags
  • Female
  • Finland
  • Founder Effect
  • Gene Expression Profiling
  • Genetic Linkage / genetics*
  • Haplotypes / genetics
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Retina / metabolism
  • Retinal Degeneration / genetics*
  • Syndrome


  • CLRN1 protein, human
  • Membrane Proteins
  • RNA, Messenger

Associated data

  • GENBANK/AC011103
  • GENBANK/AC020636
  • GENBANK/AF002986
  • GENBANK/AF132033
  • GENBANK/AF388364
  • GENBANK/AF388365
  • GENBANK/AF388366
  • GENBANK/AF388367
  • GENBANK/AF388368
  • GENBANK/AF411849
  • GENBANK/W27577
  • OMIM/276901
  • OMIM/276903
  • OMIM/276904
  • OMIM/601067
  • OMIM/602083
  • RefSeq/NM_005120
  • RefSeq/NM_014879