Document Detail

Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B.
MedLine Citation:
PMID:  23252888     Owner:  NLM     Status:  MEDLINE    
Niemann-Pick disease (NPD) types A and B are autosomal, recessively inherited, lysosomal storage disorders caused by deficient activity of acid sphingomyelinase (E.C. 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.
P Irun; M Mallén; C Dominguez; V Rodriguez-Sureda; L A Alvarez-Sala; N Arslan; N Bermejo; C Guerrero; I Perez de Soto; L Villalón; P Giraldo; M Pocovi
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-04
Journal Detail:
Title:  Clinical genetics     Volume:  84     ISSN:  1399-0004     ISO Abbreviation:  Clin. Genet.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-16     Completed Date:  2014-04-08     Revised Date:  2014-06-30    
Medline Journal Info:
Nlm Unique ID:  0253664     Medline TA:  Clin Genet     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  356-61     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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MeSH Terms
Amino Acid Substitution
Gene Order
Genetic Association Studies
Niemann-Pick Diseases / diagnosis*,  genetics*
Sphingomyelin Phosphodiesterase / genetics*
Reg. No./Substance:
EC Phosphodiesterase; EC phosphodiesterase 1, human

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