Mutations in the lipoma HMGIC fusion partner-like 5 (LHFPL5) gene cause autosomal recessive nonsyndromic hearing loss.
In two large Turkish consanguineous families, a locus for autosomal recessive nonsyndromic hearing loss (ARNSHL) was mapped to chromosome 6p21.3 by genome-wide linkage analysis in an interval overlapping with the loci DFNB53 (COL11A2), DFNB66, and DFNB67. Fine mapping excluded DFNB53 and subsequently homozygous mutations were identified in the lipoma HMGIC fusion partner-like 5 (LHFPL5) gene, also named tetraspan membrane protein of hair cell stereocilia (TMHS) gene, which was recently shown to be mutated in the "hurry scurry" mouse and in two DFNB67-linked families from Pakistan. In one family, we found a homozygous one-base pair deletion, c.649delG (p.Glu216ArgfsX26) and in the other family we identified a homozygous transition c.494C>T (p.Thr165Met). Further screening of index patients from 96 Turkish ARNSHL families and 90 Dutch ARNSHL patients identified one additional Turkish family carrying the c.649delG mutation. Haplotype analysis revealed that the c.649delG mutation was located on a common haplotype in both families. Mutation screening of the LHFPL5 homologs LHFPL3 and LHFPL4 did not reveal any disease causing mutation. Our findings indicate that LHFPL5 is essential for normal function of the human cochlea.
Kalay
Ersan
E
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Li
Yun
Y
Uzumcu
Abdullah
A
Uyguner
Oya
O
Collin
Rob W
RW
Caylan
Refik
R
Ulubil-Emiroglu
Melike
M
Kersten
Ferry F J
FF
Hafiz
Gunter
G
van Wijk
Erwin
E
Kayserili
Hulya
H
Rohmann
Edyta
E
Wagenstaller
Janine
J
Hoefsloot
Lies H
LH
Strom
Tim M
TM
Nürnberg
Gudrun
G
Baserer
Nermin
N
den Hollander
Anneke I
AI
Cremers
Frans P M
FP
Cremers
Cor W R J
CW
Becker
Christian
C
Brunner
Han G
HG
Nürnberg
Peter
P
Karaguzel
Ahmet
A
Basaran
Seher
S
Kubisch
Christian
C
Kremer
Hannie
H
Wollnik
Bernd
B
D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D008040:Genetic Linkage; D006239:Haplotypes; D006312:Hearing Loss, Bilateral / Q000175:diagnosis / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D016415:Sequence Alignment
D008565:Membrane Proteins