Schuchman E H, Miranda S R
Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Genet Test. 1997;1(1):13-9. doi: 10.1089/gte.1997.1.13.
Niemann-Pick Disease (NPD) is an autosomal recessive lysosomal storage disorder caused by a deficiency of acid sphingomyelinase (ASM). NPD occurs in two forms, neuronopathic Type A and nonneuronopathic Type B. The incidence of Type A NPD is highest among Ashkenazi Jews. Type B NPD is more common in non-Jews but has been reported in Ashkenazi Jews. Different mutations in ASM are presumed to be responsible for the different NPD phenotypes. Three mutations are predicted to account for > 95% of all Type A NPD chromosomes among Ashkenazi Jews (L302P, R496L, fsP330). Based on limited screens for these mutations among Ashkenazi Jews, a carrier frequency for Type A NPD of 1:90 is reported for this population. Less is known about mutations responsible for Type B NPD, although one mutation (delta R608) has been identified in both Ashkenazi Jews and non-Jews. Screening of the Ashkenazi Jewish population to detect > 95% of NPD carriers can be accomplished with a four-mutation panel that includes L302P, R496L, fsP330, and delta R608, the three predominant Type A mutations and one recurrent Type B mutation.
尼曼-皮克病（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。NPD有两种形式，即神经病变型A型和非神经病变型B型。A型NPD的发病率在德系犹太人中最高。B型NPD在非犹太人中更为常见，但在德系犹太人中也有报道。ASM中的不同突变被认为是导致不同NPD表型的原因。据推测，三种突变占德系犹太人中所有A型NPD染色体的95%以上（L302P、R496L、fsP330）。基于对德系犹太人中这些突变的有限筛查，该人群中A型NPD的携带频率报告为1:90。对于导致B型NPD的突变了解较少，尽管在德系犹太人和非犹太人中都发现了一种突变（delta R608）。通过包含L302P、R496L、fsP330和delta R608这四种突变的检测板，可以对德系犹太人群体进行筛查，以检测出95%以上的NPD携带者，这四种突变包括三种主要的A型突变和一种反复出现的B型突变。
