Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease.

ABSTRACT: Types A and B Niemann-Pick disease (NPD) result from the deficient activity of acid sphingomyelinase (ASM), due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene. Here we report the identification, characterization and genotype/phenotype correlations of eight novel mutations in six unrelated NPD patients. These mutations included seven missense mutations: c.631T>C (p.W211R), c.757G>C (p.D253H), c.940G>A (p.V314M), c.1280A>G (p.H427R), c.1564A>G (p.N522S), c.1575G>C (p.Q525H) and c.1729A>G (p.H577R), and a novel frameshift mutation, c.1657delACCGCCT (fsT553). Each missense mutation was expressed in 293T or COS-7 cells; mutant enzymes p.W211R, p.D253H, p.H427R and p.H577R had <1% of expressed wild-type activity, whereas p.V314M, p.N522S and p.Q525H had 21.7%, 10.1% and 64% o

SUBMITTER: Desnick JP 

PROVIDER: S-EPMC2896470 | biostudies-literature | 2010 Jul-Aug

REPOSITORIES: biostudies-literature