PMID- 10571947
OWN - NLM
STAT- MEDLINE
DCOM- 20000124
LR  - 20101118
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 14
IP  - 6
DP  - 1999
TI  - Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive
      hearing loss.
PG  - 493-501
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 straight theta = 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 beta 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.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - Talebizadeh, Z
AU  - Talebizadeh Z
AD  - Center for Hereditary Communication Disorders, Boys Town National Research
      Hospital, Omaha, Nebraska. talebiz@boystown.org
FAU - Kelley, P M
AU  - Kelley PM
FAU - Askew, J W
AU  - Askew JW
FAU - Beisel, K W
AU  - Beisel KW
FAU - Smith, S D
AU  - Smith SD
LA  - eng
GR  - P60 DC00982/DC/NIDCD NIH HHS/United States
GR  - R01 DC02942-02/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (KCNQ Potassium Channels)
RN  - 0 (KCNQ4 protein, human)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Chromosomes, Human, Pair 1/genetics
MH  - DNA/genetics
MH  - DNA Mutational Analysis
MH  - Female
MH  - Genes, Dominant
MH  - Genes, Recessive
MH  - Genetic Linkage
MH  - Genetic Variation
MH  - Hearing Loss, Sensorineural/*genetics
MH  - Humans
MH  - KCNQ Potassium Channels
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Pedigree
MH  - Point Mutation
MH  - Polymorphism, Genetic
MH  - Potassium Channels/chemistry/*genetics
MH  - *Potassium Channels, Voltage-Gated
MH  - Protein Structure, Secondary
MH  - Sequence Homology, Amino Acid
EDAT- 1999/11/26 00:00
MHDA- 1999/11/26 00:01
CRDT- 1999/11/26 00:00
PHST- 1999/11/26 00:00 [pubmed]
PHST- 1999/11/26 00:01 [medline]
PHST- 1999/11/26 00:00 [entrez]
AID - 10.1002/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P [pii]
AID - 10.1002/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P [doi]
PST - ppublish
SO  - Hum Mutat. 1999;14(6):493-501. doi:
      10.1002/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P.