title: Niemann-Pick disease: mutation update, genotype/phenotype correlations, and prospects for genetic testing.
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 (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.
authors.affiliation: Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Schuchman
authors.forename: S R
authors.initials: SR
authors.lastname: Miranda
mesh_terms: D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D009154:Mutation; D009542:Niemann-Pick Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D017931:DNA Primers