SMPD1 Mutation Update: Database and Comprehensive Analysis of Published and Novel Variants

Stefania Zampieri, Mirella Filocamo, Annalisa Pianta, Susanna Lualdi, Laura Gort, Maria Jose Coll, Richard Sinnott, Tarekegn Geberhiwot, Bruno Bembi, Andrea Dardis

Research output: Contribution to journalArticlepeer-review


Niemann-Pick Types A and B (NPA/B) diseases are autosomal recessive lysosomal storage disorders caused by the deficient activity of acid sphingomyelinase (ASM) because of the mutations in the SMPD1 gene. Here, we provide a comprehensive updated review of already reported and newly identified SMPD1 variants. Among them, 185 have been found in NPA/B patients. Disease-causing variants are equally distributed along the SMPD1 gene; most of them are missense (65.4%) or frameshift (19%) mutations. The most frequently reported mutation worldwide is the p.R610del, clearly associated with an attenuated NP disease type B phenotype. The available information about the impact of 52 SMPD1 variants on ASM mRNA and/or enzymatic activity has been collected and whenever possible, phenotype/genotype correlations were established. In addition, we created a locus-specific database easily accessible at that catalogs the 417 SMPD1 variants reported to date and provides data on their in silico predicted effects on ASM protein function or mRNA splicing. The information reviewed in this article, providing new insights into the genotype/phenotype correlation, is extremely valuable to facilitate diagnosis and genetic counseling of families affected by NPA/B.

Original languageEnglish
Pages (from-to)139-47
Number of pages9
JournalHuman Mutation
Issue number2
Publication statusPublished - Feb 2016


  • Databases, Genetic
  • Exons
  • Gene Expression
  • Genes, Recessive
  • Genetic Association Studies
  • Genotype
  • Humans
  • Introns
  • Mutation
  • Niemann-Pick Disease, Type A
  • Niemann-Pick Disease, Type B
  • Open Reading Frames
  • Phenotype
  • RNA Splicing
  • RNA, Messenger
  • Sphingomyelin Phosphodiesterase
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Review

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