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A novel DFNB31 mutation associated with Usher type 2 syndrome showing variable degrees of auditory loss in a consanguineous Portuguese family.
- Source :
-
Molecular vision [Mol Vis] 2011; Vol. 17, pp. 1598-606. Date of Electronic Publication: 2011 Jun 15. - Publication Year :
- 2011
-
Abstract
- Purpose: To identify the genetic defect of a consanguineous Portuguese family with rod-cone dystrophy and varying degrees of decreased audition.<br />Methods: A detailed ophthalmic and auditory examination was performed on a Portuguese patient with severe autosomal recessive rod-cone dystrophy. Known genetic defects were excluded by performing autosomal recessive retinitis pigmentosa (arRP) genotyping microarray analysis and by Sanger sequencing of the coding exons and flanking intronic regions of eyes shut homolog-drosophila (EYS) and chromosome 2 open reading frame 71 (C2orf71). Subsequently, genome-wide homozygosity mapping was performed in DNA samples from available family members using a 700K single nucleotide polymorphism (SNP) microarray. Candidate genes present in the significantly large homozygous regions were screened for mutations using Sanger sequencing.<br />Results: The largest homozygous region (~11 Mb) in the affected family members was mapped to chromosome 9, which harbors deafness, autosomal recessive 31 (DFNB31; a gene previously associated with Usher syndrome). Mutation analysis of DFNB31 in the index patient identified a novel one-base-pair deletion (c.737delC), which is predicted to lead to a truncated protein (p.Pro246HisfsX13) and co-segregated with the disease in the family. Ophthalmic examination of the index patient and the affected siblings showed severe rod-cone dystrophy. Pure tone audiometry revealed a moderate hearing loss in the index patient, whereas the affected siblings were reported with more profound and early onset hearing impairment.<br />Conclusions: We report a novel truncating mutation in DFNB31 associated with severe rod-cone dystrophy and varying degrees of hearing impairment in a consanguineous family of Portuguese origin. This is the second report of DFNB31 implication in Usher type 2.
- Subjects :
- Adult
Age of Onset
Base Sequence
Chromosome Mapping
Consanguinity
DNA Mutational Analysis
Female
Genes, Recessive
Genotype
Hearing Loss pathology
Homozygote
Humans
Male
Membrane Proteins metabolism
Middle Aged
Molecular Sequence Data
Mutation, Missense
Oligonucleotide Array Sequence Analysis
Pedigree
Phenotype
Polymorphism, Single Nucleotide
Portugal
Retinitis Pigmentosa pathology
Severity of Illness Index
Usher Syndromes pathology
Vision Tests
Hearing Loss genetics
Membrane Proteins genetics
Retinitis Pigmentosa genetics
Usher Syndromes genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-0535
- Volume :
- 17
- Database :
- MEDLINE
- Journal :
- Molecular vision
- Publication Type :
- Academic Journal
- Accession number :
- 21738389