Abstract
Analysis of genotyping of a five-generation American family with nonsyndromic dominant progressive hearing loss indicated linkage to the DFNA2 locus on chromosome 1p34. This kindred consists of 170 individuals, of which 51 are affected. Pure tone audiograms, medical records, and blood samples were obtained from 36 family members. Linkage analysis with five microsatellite markers spanning the region around DFNA2 produced a lod score of 6.6 for the marker MYCL1 at θ = 0.0. Hearing loss in this family showed a very similar pattern as the first reported American family with the same linkage. High frequency hearing loss was detectable as early as 3 years of age, and progressed to severe to profound loss by the fourth decade. Using intronic primers, we screened the coding region of the KCNQ4 gene. Heteroduplex analysis followed by direct sequencing identified a T→C transition at position 842, which would produce an L281S amino acid substitution. The observed mutation was shown to segregate completely with affected status in this family. The L281 residue is significantly conserved among the other members of the voltage-gated K+ channel genes superfamily. Hydrophobicity analysis indicated that L281S substitution would lower formation of the β structure at the P region of this ion channel. Mutation analysis of KCNQ4 was also performed on 80 unrelated probands from families with recessive or dominant nonsyndromic hearing loss. None of these cases showed a truncated mutation in KCNQ4.
| Original language | English |
|---|---|
| Pages (from-to) | 493-501 |
| Number of pages | 9 |
| Journal | Human Mutation |
| Volume | 14 |
| Issue number | 6 |
| DOIs | |
| State | Published - 1999 |
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All Science Journal Classification (ASJC) codes
- Genetics
- Genetics(clinical)
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Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss. / Talebizadeh, Zohreh; Kelley, Philip M.; Askew, James W.; Beisel, Kirk; Smith, Shelley D.
In: Human Mutation, Vol. 14, No. 6, 1999, p. 493-501.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss
AU - Talebizadeh, Zohreh
AU - Kelley, Philip M.
AU - Askew, James W.
AU - Beisel, Kirk
AU - Smith, Shelley D.
PY - 1999
Y1 - 1999
N2 - Analysis of genotyping of a five-generation American family with nonsyndromic dominant progressive hearing loss indicated linkage to the DFNA2 locus on chromosome 1p34. This kindred consists of 170 individuals, of which 51 are affected. Pure tone audiograms, medical records, and blood samples were obtained from 36 family members. Linkage analysis with five microsatellite markers spanning the region around DFNA2 produced a lod score of 6.6 for the marker MYCL1 at θ = 0.0. Hearing loss in this family showed a very similar pattern as the first reported American family with the same linkage. High frequency hearing loss was detectable as early as 3 years of age, and progressed to severe to profound loss by the fourth decade. Using intronic primers, we screened the coding region of the KCNQ4 gene. Heteroduplex analysis followed by direct sequencing identified a T→C transition at position 842, which would produce an L281S amino acid substitution. The observed mutation was shown to segregate completely with affected status in this family. The L281 residue is significantly conserved among the other members of the voltage-gated K+ channel genes superfamily. Hydrophobicity analysis indicated that L281S substitution would lower formation of the β structure at the P region of this ion channel. Mutation analysis of KCNQ4 was also performed on 80 unrelated probands from families with recessive or dominant nonsyndromic hearing loss. None of these cases showed a truncated mutation in KCNQ4.
AB - Analysis of genotyping of a five-generation American family with nonsyndromic dominant progressive hearing loss indicated linkage to the DFNA2 locus on chromosome 1p34. This kindred consists of 170 individuals, of which 51 are affected. Pure tone audiograms, medical records, and blood samples were obtained from 36 family members. Linkage analysis with five microsatellite markers spanning the region around DFNA2 produced a lod score of 6.6 for the marker MYCL1 at θ = 0.0. Hearing loss in this family showed a very similar pattern as the first reported American family with the same linkage. High frequency hearing loss was detectable as early as 3 years of age, and progressed to severe to profound loss by the fourth decade. Using intronic primers, we screened the coding region of the KCNQ4 gene. Heteroduplex analysis followed by direct sequencing identified a T→C transition at position 842, which would produce an L281S amino acid substitution. The observed mutation was shown to segregate completely with affected status in this family. The L281 residue is significantly conserved among the other members of the voltage-gated K+ channel genes superfamily. Hydrophobicity analysis indicated that L281S substitution would lower formation of the β structure at the P region of this ion channel. Mutation analysis of KCNQ4 was also performed on 80 unrelated probands from families with recessive or dominant nonsyndromic hearing loss. None of these cases showed a truncated mutation in KCNQ4.
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U2 - 10.1002/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P
DO - 10.1002/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P
M3 - Article
VL - 14
SP - 493
EP - 501
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 6
ER -