The authors declare no conflict of interests related to this study.
Identification of seven novel SMPD1 mutations causing Niemann–Pick disease types A and B
Article first published online: 4 JAN 2013
© 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 84, Issue 4, pages 356–361, October 2013
How to Cite
Identification of seven novel SMPD1 mutations causing Niemann–Pick disease types A and B., , , , , , , , , , , .
- Issue published online: 11 SEP 2013
- Article first published online: 4 JAN 2013
- Accepted manuscript online: 17 DEC 2012 12:34PM EST
- Manuscript Revised: 10 DEC 2012
- Manuscript Accepted: 10 DEC 2012
- Manuscript Received: 27 SEP 2012
- Spanish Fondo de Investigaciones Sanitarias. Grant Number: FIS PS09/02556, FIS 10/01605
- Ramon Areces Foundation
- Fundación para el Estudio y Terapéutica de la Enfermedad de Gaucher (FEETEG)
- Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)
- genotype/phenotype correlations;
- Niemann–Pick disease;
Niemann–Pick disease (NPD) types A and B are autosomal, recessively inherited, lysosomal storage disorders caused by deficient activity of acid sphingomyelinase (E.C. 184.108.40.206) 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.