A canonical splice site mutation in GIPC3 causes sensorineural hearing loss in a large Pakistani family

作者：Siddiqi Saima; Ismail Muhammad; Oostrik Jaap; Munawar Saba; Mansoor Atika; Kremer Hannie; Qamar Raheel; Schraders Margit^*

来源：Journal of Human Genetics, 2014, 59(12): 683-686.

DOI：10.1038/jhg.2014.86

With homozygosity mapping we have identified two large homozygous regions on chromosome 3q13.11-q13.31 and chromosome 19p13.3-q31.32 in a large Pakistani family suffering from autosomal recessive nonsyndromic hearing impairment (arNSHI). The region on chromosome 19 overlaps with the previously described deafness loci DFNB15, DFNB72 and DFNB95. Mutations in GIPC3 have been shown to underlie the nonsyndromic hearing impairment linked to these loci. Sequence analysis of all exons and exon-intron boundaries of GIPC3 revealed a homozygous canonical splice site mutation, c.226-1G %26gt; T, in GIPC3. This is the first mutation described in GIPC3 that affects splicing. The c.226-1G %26gt; T mutation is located in the acceptor splice site of intron 1 and is predicted to affect the normal splicing of exon 2. With a minigene assay it was shown to result in the use of an alternative acceptor site in exon 2, resulting in a frameshift and a premature stop codon. This study expands the mutational spectrum of GIPC3 in arNSHI.

• 出版日期2014-12