Identification and characterization of SMPD1 mutations causing niemann-pick types A and B in Spanish patients

Laura Rodríguez-Pascau, Laura Gort, Edward H. Schuchman, Lluïsa Vilageliu, Daniel Grinberg, Amparo Chabás

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40 Scopus citations


Niemann-Pick disease (NPD) types A/B are both caused by a deficiency of lysosomal acid sphingomyelinase and display autosomal recessive inheritance. These two types of the disease were described according to the presence (type A) or absence (type B) of neurological symptoms. We present a molecular analysis of 19 Spanish NPD A/B patients and two from Maghreb. Eight of the patients had type A and 13 had type B NPD. All mutant SMPD1 alleles were identified, including 17 different mutations, 10 of which were novel. The only frequent mutations in the 21 NPD patients were c.1823-1825delGCC (p.R608del) (38%) and c.1445C > A (p.A482E) (9%). Genotype-phenotype correlations were established for most of the mutations and, in particular, the p.R608del-type B association was confirmed. This mutation accounts for 61.5% of the mutant alleles in the type B subgroup of patients. Expression studies performed on six of the identified mutations confirmed them to be disease-causing due to their low enzyme activity. An allele with a mutation affecting a noncanonical donor splice site produced only aberrant mRNAs, corresponding to previously reported nonfunctional SMPD1 minor transcripts. This study is the first exhaustive mutational analysis of Spanish Niemann-Pick A/B disease patients.

Original languageEnglish
Pages (from-to)1117-1122
Number of pages6
JournalHuman Mutation
Issue number7
StatePublished - Jul 2009


  • Acid sphingomyelinase deficiency
  • Heterologous expression
  • Niemann-Pick A/B
  • SMPD1


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