Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B


Irun P., Mallen M., Dominguez C., Rodriguez-Sureda V., Alvarez-Sala L. A., Arslan N., ...More

CLINICAL GENETICS, vol.84, no.4, pp.356-361, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 84 Issue: 4
  • Publication Date: 2013
  • Doi Number: 10.1111/cge.12076
  • Journal Name: CLINICAL GENETICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.356-361
  • Keywords: chitotriosidase, genotype, phenotype correlations, genotyping, Niemann-Pick disease, SMPD1, sphingomyelinase, ACID SPHINGOMYELINASE GENE, GENOTYPE/PHENOTYPE CORRELATIONS, INTERMEDIATE PHENOTYPE, PLASMA CHITOTRIOSIDASE, MARKED ELEVATION, GAUCHER-DISEASE, PREVALENCE, DEFICIENCY
  • Dokuz Eylül University Affiliated: Yes

Abstract

Niemann-Pick disease (NPD) types A and B are autosomal, recessively inherited, lysosomal storage disorders caused by deficient activity of acid sphingomyelinase (E.C. 3.1.4.12) because of mutations in the sphingomyelin phosphodiesterase-1 (SMPD1) gene. Here, we present the molecular analysis and clinical characteristics of 15 NPD type A and B patients. Sequencing the SMDP1 gene revealed eight previously described mutations and seven novel mutations including four missense [c.682T>C (p.Cys228Arg), c.1159T>C (p.Cys387Arg), c.1474G>A (p.Gly492Ser), and c.1795C>T (p.Leu599Phe)], one frameshift [c.169delG (p.Ala57Leufs*20)] and two splicing (c.316+1G>T and c.1341delG). The most frequent mutations were p.Arg610del (21%) and p.Gly247Ser (12%). Two patients homozygous for p.Arg610del and initially classified as phenotype B showed different clinical manifestations. Patients homozygous for p.Leu599Phe had phenotype B, and those homozygous for c.1341delG or c.316+1G>T presented phenotype A. The present results provide new insight into genotype/phenotype correlations in NPD and emphasize the difficulty of classifying patients into types A and B, supporting the idea of a continuum between these two classic phenotypes.