Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease.

Types A and B Niemann-Pick disease (NPD), an autosomal recessive lysosomal storage disorder, are caused by deficiency of acid sphingomyelinase (ASM). The recent identification of mutations in ASM gene causing types A and B NPD has led to the investigation of the phenotypic heterogeneity and the ethnic distribution of this disease, especially in Ashkenazi Jewish population. To characterize the mutations causing NPD in Japanese population, we analyzed the genomic sequence of ASM from a Japanese patient with type A NPD by PCR amplification and sequencing. A new mutation, Y446C, was identified. The authenticity of this lesion was demonstrated by the expression of the Y446C allele in COS-1 cells. No residual ASM activity was detected from the expression of the Y446C.