Imprinting at the SMPD1 locus: implications for acid sphingomyelinase-deficient Niemann-Pick disease.

ABSTRACT: Acid sphingomyelinase (ASM) is the lipid hydrolase that is deficient in types A and B Niemann-Pick disease (NPD). Here, we demonstrate that the gene encoding ASM (SMPD1) is paternally imprinted and that differential expression of the mutant alleles in patients with ASM-deficient NPD and in carriers influences the disease phenotype. Comparison of the results of genomic sequencing versus reverse-transcriptase polymerase chain reaction sequencing for several patients with NPD revealed preferential expression of one mutant allele. Further analysis of one family showed that the expressed allele was maternally inherited and that the distinct clinical presentations of the individual patients were correlated with the amount of residual ASM activity expressed from the maternal mutation. Treatment o

SUBMITTER: Simonaro CM 

PROVIDER: S-EPMC1474038 | biostudies-literature | 2006 May

REPOSITORIES: biostudies-literature