title: Alleged Detrimental Mutations in the SMPD1 Gene in Patients with Niemann-Pick Disease.
abstract: Loss-of-function mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene are associated with decreased catalytic activity of acid sphingomyelinase (ASM) and are the cause of the autosomal recessive lysosomal storage disorder Niemann-Pick disease (NPD) types A and B. Currently, >100 missense mutations in SMPD1 are listed in the Human Gene Mutation Database. However, not every sequence variation in SMPD1 is detrimental and gives rise to NPD. We have analysed several alleged SMPD1 missense mutations mentioned in a recent publication and found them to be common variants of SMPD1 that give rise to normal in vivo and in vitro ASM activity. (Comment on Manshadi et al. Int. J. Mol. Sci. 2015, 16, 6668-6676).
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany. cosima.rhein@uk-erlangen.de.
authors.forename: Cosima
authors.initials: C
authors.lastname: Rhein
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany. christiane.muehle@uk-erlangen.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Mühle
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany. johannes.kornhuber@uk-erlangen.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany. martin.reichel@uk-erlangen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Reichel
mesh_terms: D006801:Humans; D009154:Mutation; D052536:Niemann-Pick Disease, Type A / Q000235:genetics*; D052537:Niemann-Pick Disease, Type B / Q000235:genetics*; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*
chemical_list: D013108:Sphingomyelin Phosphodiesterase
keywords: Niemann-Pick disease; gene variant; missense mutation; polymorphism; sphingomyelin phosphodiesterase