Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - Implications for genetic testing

Tim Hutchin, N. N. Coy, H. Conlon, E. Telford, K. Bromelow, D. Blaydon, G. Taylor, E. Coghill, S. Brown, R. Trembath, Xue Z Liu, M. Bitner-Glindzicz, R. Mueller

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Approximately one in 2000 children is born with a genetic hearing impairment, mostly inherited as a non-syndromic, autosomal recessive trait, for which more than 30 different genes have been identified. Previous studies have shown that one of these genes, connexin 26 (GJB2), accounts for 30-60% of such deafness, but the relative contribution of the many other genes is not known, especially in the outbred UK population. This lack of knowledge hampers the development of diagnostic genetic services for deafness. In an effort to determine the molecular aetiology of deafness, in the population, 142 sib pairs with early-onset, non-syndromic hearing impairment were recruited. Those in whom deafness could not be attributed to GJB2 mutations were investigated further for other mapped genes. The genetic basis of 55 cases (38.7%) was established, 33.1% being due to mutations in the GJB2 gene and 3.5% due to mutations in SLC26A4. None of the remaining 26 loci investigated made a significant contribution to deafness in a Caucasian population. We suggest that screening the GJB2 and SLC26A4 genes should form the basis of any genetic testing programme for childhood deafness and highlight a number of important issues for consideration and future work.

Original languageEnglish
Pages (from-to)506-512
Number of pages7
JournalClinical Genetics
Volume68
Issue number6
DOIs
StatePublished - Dec 1 2005

Fingerprint

Genetic Testing
Deafness
Genes
Hearing Loss
Mutation
Genetic Services
Diagnostic Services
Population

Keywords

  • Deafness
  • Genetics
  • Mutations
  • Recessive

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - Implications for genetic testing. / Hutchin, Tim; Coy, N. N.; Conlon, H.; Telford, E.; Bromelow, K.; Blaydon, D.; Taylor, G.; Coghill, E.; Brown, S.; Trembath, R.; Liu, Xue Z; Bitner-Glindzicz, M.; Mueller, R.

In: Clinical Genetics, Vol. 68, No. 6, 01.12.2005, p. 506-512.

Research output: Contribution to journalArticle

Hutchin, T, Coy, NN, Conlon, H, Telford, E, Bromelow, K, Blaydon, D, Taylor, G, Coghill, E, Brown, S, Trembath, R, Liu, XZ, Bitner-Glindzicz, M & Mueller, R 2005, 'Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - Implications for genetic testing', Clinical Genetics, vol. 68, no. 6, pp. 506-512. https://doi.org/10.1111/j.1399-0004.2005.00539.x
Hutchin, Tim ; Coy, N. N. ; Conlon, H. ; Telford, E. ; Bromelow, K. ; Blaydon, D. ; Taylor, G. ; Coghill, E. ; Brown, S. ; Trembath, R. ; Liu, Xue Z ; Bitner-Glindzicz, M. ; Mueller, R. / Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - Implications for genetic testing. In: Clinical Genetics. 2005 ; Vol. 68, No. 6. pp. 506-512.
@article{68c41f3f69304440aaf19251e7215cae,
title = "Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - Implications for genetic testing",
abstract = "Approximately one in 2000 children is born with a genetic hearing impairment, mostly inherited as a non-syndromic, autosomal recessive trait, for which more than 30 different genes have been identified. Previous studies have shown that one of these genes, connexin 26 (GJB2), accounts for 30-60{\%} of such deafness, but the relative contribution of the many other genes is not known, especially in the outbred UK population. This lack of knowledge hampers the development of diagnostic genetic services for deafness. In an effort to determine the molecular aetiology of deafness, in the population, 142 sib pairs with early-onset, non-syndromic hearing impairment were recruited. Those in whom deafness could not be attributed to GJB2 mutations were investigated further for other mapped genes. The genetic basis of 55 cases (38.7{\%}) was established, 33.1{\%} being due to mutations in the GJB2 gene and 3.5{\%} due to mutations in SLC26A4. None of the remaining 26 loci investigated made a significant contribution to deafness in a Caucasian population. We suggest that screening the GJB2 and SLC26A4 genes should form the basis of any genetic testing programme for childhood deafness and highlight a number of important issues for consideration and future work.",
keywords = "Deafness, Genetics, Mutations, Recessive",
author = "Tim Hutchin and Coy, {N. N.} and H. Conlon and E. Telford and K. Bromelow and D. Blaydon and G. Taylor and E. Coghill and S. Brown and R. Trembath and Liu, {Xue Z} and M. Bitner-Glindzicz and R. Mueller",
year = "2005",
month = "12",
day = "1",
doi = "10.1111/j.1399-0004.2005.00539.x",
language = "English",
volume = "68",
pages = "506--512",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - Implications for genetic testing

AU - Hutchin, Tim

AU - Coy, N. N.

AU - Conlon, H.

AU - Telford, E.

AU - Bromelow, K.

AU - Blaydon, D.

AU - Taylor, G.

AU - Coghill, E.

AU - Brown, S.

AU - Trembath, R.

AU - Liu, Xue Z

AU - Bitner-Glindzicz, M.

AU - Mueller, R.

PY - 2005/12/1

Y1 - 2005/12/1

N2 - Approximately one in 2000 children is born with a genetic hearing impairment, mostly inherited as a non-syndromic, autosomal recessive trait, for which more than 30 different genes have been identified. Previous studies have shown that one of these genes, connexin 26 (GJB2), accounts for 30-60% of such deafness, but the relative contribution of the many other genes is not known, especially in the outbred UK population. This lack of knowledge hampers the development of diagnostic genetic services for deafness. In an effort to determine the molecular aetiology of deafness, in the population, 142 sib pairs with early-onset, non-syndromic hearing impairment were recruited. Those in whom deafness could not be attributed to GJB2 mutations were investigated further for other mapped genes. The genetic basis of 55 cases (38.7%) was established, 33.1% being due to mutations in the GJB2 gene and 3.5% due to mutations in SLC26A4. None of the remaining 26 loci investigated made a significant contribution to deafness in a Caucasian population. We suggest that screening the GJB2 and SLC26A4 genes should form the basis of any genetic testing programme for childhood deafness and highlight a number of important issues for consideration and future work.

AB - Approximately one in 2000 children is born with a genetic hearing impairment, mostly inherited as a non-syndromic, autosomal recessive trait, for which more than 30 different genes have been identified. Previous studies have shown that one of these genes, connexin 26 (GJB2), accounts for 30-60% of such deafness, but the relative contribution of the many other genes is not known, especially in the outbred UK population. This lack of knowledge hampers the development of diagnostic genetic services for deafness. In an effort to determine the molecular aetiology of deafness, in the population, 142 sib pairs with early-onset, non-syndromic hearing impairment were recruited. Those in whom deafness could not be attributed to GJB2 mutations were investigated further for other mapped genes. The genetic basis of 55 cases (38.7%) was established, 33.1% being due to mutations in the GJB2 gene and 3.5% due to mutations in SLC26A4. None of the remaining 26 loci investigated made a significant contribution to deafness in a Caucasian population. We suggest that screening the GJB2 and SLC26A4 genes should form the basis of any genetic testing programme for childhood deafness and highlight a number of important issues for consideration and future work.

KW - Deafness

KW - Genetics

KW - Mutations

KW - Recessive

UR - http://www.scopus.com/inward/record.url?scp=28644439243&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28644439243&partnerID=8YFLogxK

U2 - 10.1111/j.1399-0004.2005.00539.x

DO - 10.1111/j.1399-0004.2005.00539.x

M3 - Article

C2 - 16283880

AN - SCOPUS:28644439243

VL - 68

SP - 506

EP - 512

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 6

ER -