Mutations in TPRN cause a progressive form of autosomal-recessive nonsyndromic hearing loss.
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.
Li
Yun
Y
Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.
Pohl
Esther
E
Boulouiz
Redouane
R
Schraders
Margit
M
Nürnberg
Gudrun
G
Charif
Majida
M
Admiraal
Ronald J C
RJ
von Ameln
Simon
S
Baessmann
Ingelore
I
Kandil
Mostafa
M
Veltman
Joris A
JA
Nürnberg
Peter
P
Kubisch
Christian
C
Barakat
Abdelhamid
A
Kremer
Hannie
H
Wollnik
Bernd
B
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
D017931:DNA Primers; D011506:Proteins; C548551:TPRN protein, human; D004247:DNA