Mutations in TPRN Cause a Progressive Form of Autosomal-Recessive Nonsyndromic Hearing Loss

作者：Li Yun; Pohl Esther; Boulouiz Redouane; Schraders Margit; Nuernberg Gudrun; Charif Majida; Admiraal Ronald J C; von Ameln Simon; Baessmann Ingelore; Kandil Mostafa; Veltman Joris A; Nuernberg Peter; Kubisch Christian; Barakat Abdelhamid; Kremer Hannie; Wolinik Bernd^*

来源：American Journal of Human Genetics, 2010, 86(3): 479-484.

DOI：10.1016/j.ajhg.2010.02.003

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 fort-nation. 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.

• 出版日期2010-3-12