Niemann–Pick Disease: Mutation Update, Genotype/Phenotype Correlations, and Prospects for Genetic Testing
- 1 January 1997
- journal article
- review article
- Published by Mary Ann Liebert Inc in Genetic Testing
- Vol. 1 (1) , 13-19
- https://doi.org/10.1089/gte.1997.1.13
Abstract
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 (ΔR608) 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 ΔAR608, the three predominant Type A mutations and one recurrent Type B mutation.Keywords
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