Mutations in GJB2, GJB6, and mitochondrial DNA are rare in African American and Caribbean Hispanic individuals with hearing impairment

Joy Samanich, Christina Lowes, Robert D. Burk, Sara Shanske, J. Lu, Alan Shanske, Bernice E. Morrow

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Autosomal recessive nonsyndromic sensorineural hearing impairment (ARNSHI) comprises 80% of familial hearing loss cases. Approximately half result from mutations in the connexin 26 (Cx26) gene, GJB2, in Caucasian populations. Heterozygous mutations in GJB2 occasionally co-occur with a deletion of part of GJB6 (connexin 30; Cx30). It is estimated that approximately 1% of deafness is maternally inherited, due to mutations in mitochondrial DNA (mtDNA). Few studies have focused on the frequency of mutations in connexins or mtDNA in African American (AA) and Caribbean Hispanic (CH) admixture populations. In this study, we performed bidirectional sequencing of the GJB2 gene and polymerase chain reaction (PCR) screening for the common GJB6 deletion, as well as PCR/RFLP analysis for three mutations in mtDNA (A1555G, A3243G, A7445G), in 109 predominantly simplex AA and CH individuals. Variations found were a 101T > C (M34T; 1/101 cases), 109G > A (V37I; 1/101), 35delG (mutation; 4/101, 3/4 of non-AA/CH ethnicity), 167delT (mutation; 1/101), 139G > T (mutation; E47X; 1/101 homozygote, consanguineous), -15C > T (1/101), 79G > A (V27I; 9/101), 380G > A (R127H; 4/101; Guyana, India, Pakistan ethnicity), 670A > C (Indeterminate; K224Q; 1/101), 503A > G (novel; K168R; 3/101) and 684C > A (novel; 1/101). All but one of the AA and CH patients had monoallelic variations. There were no hemizygous GJB6 deletions in those with monoallelic GJB2 variations. We also did not identify any patients with the three mutations in mtDNA. Bidirectional sequencing of the GJB2 gene was performed in 187 AA and Hispanic healthy individuals. Our results reveal that GJB2 mutations, GJB6 deletions, and mtDNA mutations may not be significant in these minority admixture populations.

Original languageEnglish (US)
Pages (from-to)830-838
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Volume143
Issue number8
DOIs
StatePublished - Apr 15 2007

Fingerprint

Mitochondrial DNA
Hearing Loss
Hispanic Americans
African Americans
Mutation
Connexins
Guyana
Population
Genes
Polymerase Chain Reaction
Sequence Deletion
Pakistan
Homozygote
Deafness
Mutation Rate
Restriction Fragment Length Polymorphisms
India

Keywords

  • Admixture populations
  • African American
  • Connexin 26
  • Connexin 30
  • Deafness
  • Gene frequency
  • Genetics
  • GJB2
  • GJB6
  • Hearing loss
  • Hispanic
  • Mitochondrial mutations
  • Mutation

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Mutations in GJB2, GJB6, and mitochondrial DNA are rare in African American and Caribbean Hispanic individuals with hearing impairment. / Samanich, Joy; Lowes, Christina; Burk, Robert D.; Shanske, Sara; Lu, J.; Shanske, Alan; Morrow, Bernice E.

In: American Journal of Medical Genetics, Part A, Vol. 143, No. 8, 15.04.2007, p. 830-838.

Research output: Contribution to journalArticle

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AU - Shanske, Alan

AU - Morrow, Bernice E.

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AB - Autosomal recessive nonsyndromic sensorineural hearing impairment (ARNSHI) comprises 80% of familial hearing loss cases. Approximately half result from mutations in the connexin 26 (Cx26) gene, GJB2, in Caucasian populations. Heterozygous mutations in GJB2 occasionally co-occur with a deletion of part of GJB6 (connexin 30; Cx30). It is estimated that approximately 1% of deafness is maternally inherited, due to mutations in mitochondrial DNA (mtDNA). Few studies have focused on the frequency of mutations in connexins or mtDNA in African American (AA) and Caribbean Hispanic (CH) admixture populations. In this study, we performed bidirectional sequencing of the GJB2 gene and polymerase chain reaction (PCR) screening for the common GJB6 deletion, as well as PCR/RFLP analysis for three mutations in mtDNA (A1555G, A3243G, A7445G), in 109 predominantly simplex AA and CH individuals. Variations found were a 101T > C (M34T; 1/101 cases), 109G > A (V37I; 1/101), 35delG (mutation; 4/101, 3/4 of non-AA/CH ethnicity), 167delT (mutation; 1/101), 139G > T (mutation; E47X; 1/101 homozygote, consanguineous), -15C > T (1/101), 79G > A (V27I; 9/101), 380G > A (R127H; 4/101; Guyana, India, Pakistan ethnicity), 670A > C (Indeterminate; K224Q; 1/101), 503A > G (novel; K168R; 3/101) and 684C > A (novel; 1/101). All but one of the AA and CH patients had monoallelic variations. There were no hemizygous GJB6 deletions in those with monoallelic GJB2 variations. We also did not identify any patients with the three mutations in mtDNA. Bidirectional sequencing of the GJB2 gene was performed in 187 AA and Hispanic healthy individuals. Our results reveal that GJB2 mutations, GJB6 deletions, and mtDNA mutations may not be significant in these minority admixture populations.

KW - Admixture populations

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KW - Connexin 30

KW - Deafness

KW - Gene frequency

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KW - GJB2

KW - GJB6

KW - Hearing loss

KW - Hispanic

KW - Mitochondrial mutations

KW - Mutation

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