Takahashi T, Suchi M, Sato W, Ten S B, Sakuragawa N, Desnick R J, Schuchman E H, Takada G
Department of Pediatrics, Akita University School of Medicine, Japan.
Tohoku J Exp Med. 1995 Oct;177(2):117-23. doi: 10.1620/tjem.177.117.
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.
A型和B型尼曼-匹克病（NPD）是一种常染色体隐性溶酶体贮积症，由酸性鞘磷脂酶（ASM）缺乏引起。最近，导致A型和B型NPD的ASM基因突变的鉴定引发了对该疾病的表型异质性和种族分布的研究，尤其是在德系犹太人群体中。为了鉴定导致日本人群NPD的突变，我们通过聚合酶链反应（PCR）扩增和测序分析了一名A型NPD日本患者的ASM基因组序列。我们鉴定出了一个新的突变Y446C。通过在COS-1细胞中表达Y446C等位基因，证实了该病变的真实性。从Y446C的表达中未检测到残余的ASM活性。
