title: Mutations in TPRN cause a progressive form of autosomal-recessive nonsyndromic hearing loss.
abstract: We performed genome-wide homozygosity mapping in a large consanguineous family from Morocco and mapped the autosomal-recessive nonsyndromic hearing loss (ARNSHL) in this family to the DFNB79 locus on chromosome 9q34. By sequencing of 62 positional candidate genes of the critical region, we identified a causative homozygous 11 bp deletion, c.42_52del, in the TPRN gene in all seven affected individuals. The deletion is located in exon 1 and results in a frameshift and premature protein truncation (p.Gly15AlafsX150). Interestingly, the deleted sequence is part of a repetitive and CG-rich motive predicted to be prone to structural aberrations during crossover formation. We identified another family with progressive ARNSHL linked to this locus, whose affected members were shown to carry a causative 1 bp deletion (c.1347delG) in exon 1 of TPRN. The function of the encoded protein, taperin, is unknown; yet, partial homology to the actin-caping protein phostensin suggests a role in actin dynamics.
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Esther
authors.initials: E
authors.lastname: Pohl
authors.forename: Redouane
authors.initials: R
authors.lastname: Boulouiz
authors.forename: Margit
authors.initials: M
authors.lastname: Schraders
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nürnberg
authors.forename: Majida
authors.initials: M
authors.lastname: Charif
authors.forename: Ronald J C
authors.initials: RJ
authors.lastname: Admiraal
authors.forename: Simon
authors.initials: S
authors.lastname: von Ameln
authors.forename: Ingelore
authors.initials: I
authors.lastname: Baessmann
authors.forename: Mostafa
authors.initials: M
authors.lastname: Kandil
authors.forename: Joris A
authors.initials: JA
authors.lastname: Veltman
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Christian
authors.initials: C
authors.lastname: Kubisch
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Barakat
authors.forename: Hannie
authors.initials: H
authors.lastname: Kremer
authors.forename: Bernd
authors.initials: B
authors.lastname: Wollnik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003051:Cochlea / Q000378:metabolism; D003241:Consanguinity; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D015870:Gene Expression; D005808:Genes, Recessive; D034381:Hearing Loss / Q000151:congenital / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D009018:Morocco; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; D011506:Proteins; C548551:TPRN protein, human; D004247:DNA