Genetic analysis of a four generation Indian family with Ushersyndrome: a novel insertion mutation in MYO7A

[摘要] Purpose: Usher syndrome (USH) is a rare autosomal recessive disordercharacterized by deafness and retinitis pigmentosa. The purpose of thisstudy was to determine the genetic cause of USH in a four generationIndian family.Methods: Peripheral blood samples were collected from individualsfor genomic DNA isolation. To determine the linkage of this family toknown USH loci, microsatellite markers were selected from the candidateregions of known loci and used to genotype the family. Exon specificintronic primers for the MYO7A gene were used to amplify DNA samplesfrom one affected individual from the family. PCR products weresubsequently sequenced to detect mutation. PCR-SSCP analysis was used todetermine if the mutation segregated with the disease in the family andwas not present in 50 control individuals.Results: All affected individuals had a classic USH type I (USH1)phenotype which included deafness, vestibular dysfunction and retinitispigmentosa. Pedigree analysis suggested an autosomal recessive mode ofinheritance of USH in the family. Haplotype analysis suggested linkageof this family to the USH1B locus on chromosome 11q. DNA sequenceanalysis of the entire coding region of the MYO7A gene showed anovel insertion mutation c.2663_2664insA in a homozygous state in allaffected individuals, resulting in truncation of MYO7A protein.Conclusions: This is the first study from India which reports anovel MYO7A insertion mutation in a four generation USH family. Themutation is predicted to produce a truncated MYO7A protein. With thenovel mutation reported here, the total number of USH causing mutationsin the MYO7A gene described to date reaches to 75.

[学科分类] 生物化学/生物物理