Seven Novel Acid Sphingomyelinase Gene Mutations in Niemann-Pick Type A and B Patients


*Correspondence: Dr. Jakub Sikora, Institute of Inherited Metabolic Disorders, Div. B, Ke Karlovu 2, 128 08, Praha 2, Czech Republic. Fax: + 420/2/2491 9392. E-mail:


We have analyzed acid sphingomyelinase (SMPD1; E.C. 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.