title: Mutations in the lipoma HMGIC fusion partner-like 5 (LHFPL5) gene cause autosomal recessive nonsyndromic hearing loss.
abstract: 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.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Ersan
authors.initials: E
authors.lastname: Kalay
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Abdullah
authors.initials: A
authors.lastname: Uzumcu
authors.forename: Oya
authors.initials: O
authors.lastname: Uyguner
authors.forename: Rob W
authors.initials: RW
authors.lastname: Collin
authors.forename: Refik
authors.initials: R
authors.lastname: Caylan
authors.forename: Melike
authors.initials: M
authors.lastname: Ulubil-Emiroglu
authors.forename: Ferry F J
authors.initials: FF
authors.lastname: Kersten
authors.forename: Gunter
authors.initials: G
authors.lastname: Hafiz
authors.forename: Erwin
authors.initials: E
authors.lastname: van Wijk
authors.forename: Hulya
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authors.lastname: Kayserili
authors.forename: Edyta
authors.initials: E
authors.lastname: Rohmann
authors.forename: Janine
authors.initials: J
authors.lastname: Wagenstaller
authors.forename: Lies H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nürnberg
authors.forename: Nermin
authors.initials: N
authors.lastname: Baserer
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Cor W R J
authors.initials: CW
authors.lastname: Cremers
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.forename: Han G
authors.initials: HG
authors.lastname: Brunner
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Ahmet
authors.initials: A
authors.lastname: Karaguzel
authors.forename: Seher
authors.initials: S
authors.lastname: Basaran
authors.forename: Christian
authors.initials: C
authors.lastname: Kubisch
authors.forename: Hannie
authors.initials: H
authors.lastname: Kremer
authors.forename: Bernd
authors.initials: B
authors.lastname: Wollnik
mesh_terms: 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
chemical_list: D008565:Membrane Proteins