A canonical splice site mutation in GIPC3 causes sensorineural hearing loss in a large Pakistani family.
J Hum Genet
; 59(12): 683-6, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25296581
ABSTRACT
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>T, in GIPC3. This is the first mutation described in GIPC3 that affects splicing. The c.226-1G>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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Sítios de Splice de RNA
/
Perda Auditiva Neurossensorial
Tipo de estudo:
Etiology_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
J Hum Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Paquistão