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Novel compound heterozygous mutations in MYO7A in a Chinese family with Usher syndrome type 1.
- Source :
-
Molecular vision [Mol Vis] 2013; Vol. 19, pp. 695-701. Date of Electronic Publication: 2013 Mar 21. - Publication Year :
- 2013
-
Abstract
- Purpose: To identify the disease-causing mutation(s) in a Chinese family with autosomal recessive Usher syndrome type 1 (USH1).<br />Methods: An ophthalmic examination and an audiometric test were conducted to ascertain the phenotype of two affected siblings. The microsatellite marker D11S937, which is close to the candidate gene MYO7A (USH1B locus), was selected for genotyping. From the DNA of the proband, all coding exons and exon-intron boundaries of MYO7A were sequenced to identify the disease-causing mutation(s). Restriction fragment length polymorphism (RFLP) analysis was performed to exclude the alternative conclusion that the mutations are non-pathogenic rare polymorphisms.<br />Results: Based on severe hearing impairment, unintelligible speech, and retinitis pigmentosa, a clinical diagnosis of Usher syndrome type 1 was made. The genotyping results did not exclude the USH1B locus, which suggested that the MYO7A gene was likely the gene associated with the disease-causing mutation(s) in the family. With direct DNA sequencing of MYO7A, two novel compound heterozygous mutations (c.3742G>A and c.6051+1G>A) of MYO7A were identified in the proband. DNA sequence analysis and RFLP analysis of other family members showed that the mutations cosegregated with the disease. Unaffected members, including the parents, uncle, and sister of the proband, carry only one of the two mutations. The mutations were not present in the controls (100 normal Chinese subjects=200 chromosomes) according to the RFLP analysis.<br />Conclusions: In this study, we identified two novel mutations, c.3742G>A (p.E1248K) and c.6051+1G>A (donor splice site mutation in intron 44), of MYO7A in a Chinese non-consanguineous family with USH1. The mutations cosegregated with the disease and most likely cause the phenotype in the two affected siblings who carry these mutations compound heterozygously. Our finding expands the mutational spectrum of MYO7A.
- Subjects :
- Amino Acid Sequence
Audiometry
Base Sequence
China
DNA Mutational Analysis
Family
Female
Fundus Oculi
Genes, Recessive genetics
Genetic Predisposition to Disease
Heterozygote
Humans
Male
Molecular Sequence Data
Myosin VIIa
Myosins chemistry
Pedigree
Sequence Alignment
Asian People genetics
Mutation genetics
Myosins genetics
Usher Syndromes genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-0535
- Volume :
- 19
- Database :
- MEDLINE
- Journal :
- Molecular vision
- Publication Type :
- Academic Journal
- Accession number :
- 23559863