Document Detail

Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B.
MedLine Citation:
PMID:  23252888     Owner:  NLM     Status:  Publisher    
Niemann-Pick disease (NPD) types A and B are autosomal, recessively inherited, lysosomal storage disorders caused by deficient activity of acid sphingomyelinase (ASM, E.C. due to 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; LA 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:  JOURNAL ARTICLE     Date:  2012-12-17
Journal Detail:
Title:  Clinical genetics     Volume:  -     ISSN:  1399-0004     ISO Abbreviation:  Clin. Genet.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0253664     Medline TA:  Clin Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 John Wiley & Sons A/S.
Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón (IIS), Zaragoza, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Zaragoza, Barcelona, Spain.
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