Gluck I, Zeigler M, Bargal R, Schiff E, Bach G
Department of Human Genetics, Hadassah Hebrew University Hospital, Jerusalem 91120, Israel.
Hum Mutat. 1998;12(2):136. doi: 10.1002/(SICI)1098-1004(1998)12:2<136::AID-HUMU11>3.0.CO;2-0.
A novel single base pair deletion in the acid sphingomyelinase (ASM) gene (677delT in the cDNA) was identified in 12 Israeli Arab families with Niemann-Pick disease (NPD) type A. This deletion creates a premature stop codon which explains the complete deficiency of ASM activity in these patients and the severe clinical manifestation. A single mutation in 12 families living in a relatively small geographical region suggests a founder effect and explains the high frequency of this disease in this population. This is in contrast to multiple mutations found in two other lysosomal storage disorders prevalent in this population, namely, Hurler disease (MPSI) and metachromatic leukodystrophy. Mutations analysis is therefore an important tool in characterizing the grounds for the high frequency of inherited diseases as well as a basis for prevention programs for prevalent diseases through carrier identification and the ascertainment of high risk families.
在12个患有A型尼曼-匹克病（NPD）的以色列阿拉伯家庭中，发现了酸性鞘磷脂酶（ASM）基因中的一种新型单碱基对缺失（cDNA中的677delT）。这种缺失产生了一个提前终止密码子，这解释了这些患者中ASM活性的完全缺乏以及严重的临床表现。生活在相对较小地理区域的12个家庭中的单一突变表明存在奠基者效应，并解释了该疾病在这一人群中的高发病率。这与在该人群中普遍存在的另外两种溶酶体贮积症，即Hurler病（MPSI）和异染性脑白质营养不良中发现的多种突变形成对比。因此，突变分析是确定遗传病高发病率原因的重要工具，也是通过携带者识别和确定高危家庭来开展常见疾病预防项目的基础。
