非典型的臨床症状を示したＵＳＨ２Ａ遺伝子変異例

Abstract

Usher syndrome (USH) is an autosomal recessive disorder characterized by hearing loss and retinitis pigmentosa. USH can be classified into 3 clinical subtypes (USH type 1-3: USH1-3) on the basis of the severity and progression of hearing loss and the presence or absence of vestibular dysfunction. We conducted a mutation analysis of USH2A, one of the disease-causing genes of USH2, and identified c.8559-2A>G and p.Trp3150X in a heterozygous state in a USH patient. Though USH2 is characterized by non-progressive moderate-to-severe hearing loss and normal vestibular dysfunction, the patient showed atypical USH2 phenotype-rapidly progressive hearing loss. In atypical patients, environmental factors or modifier genes are presumed to influence the clinical findings. Because the patient had no history of noise exposure, ototoxic medication, or ultraviolet exposure, modifier genes were likely to have influenced the atypical phenotype with USH2A mutations. Considering MYO7A, CDH23, and USH3A as modifier genes, we conducted a mutation analysis of these genes. We identified 16, 44, and 2 sequence alterations in MYO7A, CDH23, and USH3A, respectively, none of which was presumed to be a mutation. Though we could not identify the causes of the atypical phenotype, we considered it very important in the expansion of the genetic analysis of USH that the causes of atypical USH patients should be identified.