title: Seven novel acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients.
abstract: We have analyzed acid sphingomyelinase (SMPD1; E.C. 3.1.4.12) gene mutations in four Niemann-Pick disease (NPD) type A and B patients of Turkish ancestry and in three patients of Dutch origin. Among four NPD type A patients we found two homozygotes for the g.1421C > T (H319Y) and g.3714T > C (Y537H) mutations and two compound heterozygotes, one for the g.3337T > C (F463S) and g.3373C > T (P475L) mutations and the other for the g.84delC (G29fsX74) and g.1208A > C (S248R) mutations. One of the type B patients was homozygous for the g.2629C>T (P371S) mutation. The last two type B patients were homozygotes for the common g.3927_3929delCGC (R608del) mutation. The G29fsX74, S248R, H319Y, P371S, F463S, P475L and Y537H SMPD1 mutations are all novel and were verified by PCR/RFLP and/or ARMS. All of the identified mutations are likely to be rare or private, with the exception of R608del which is prevalent among NPD type B patients from the North-African Maghreb region. Geographical and/or social isolation of the affected families are likely contributing factors for the high number of homozygotes in our group.
authors.affiliation: Institute of Inherited Metabolic Disorders, Charles University, 1st Faculty of Medicine, Prague, Czech Republic. jakub.sikora@l1.cuni.cz
authors.forename: J
authors.initials: J
authors.lastname: Sikora
authors.forename: H
authors.initials: H
authors.lastname: Pavlu-Pereira
authors.forename: M
authors.initials: M
authors.lastname: Elleder
authors.forename: H
authors.initials: H
authors.lastname: Roelofs
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009542:Niemann-Pick Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*
chemical_list: C112980:acid sphingomyelinase-1; D013108:Sphingomyelin Phosphodiesterase