title: Analysis of the sphingomyelin phosphodiesterase 1 gene (SMPD1) in Turkish Niemann-Pick disease patients: mutation profile and description of a novel mutation.
abstract: Niemann-Pick disease (NPD) is a lysosomal storage disorder that results from the deficiency of a lysosomal enzyme, acid sphingomyelinase. Niemann-Pick disease type A and B is caused by mutations in the sphingomyelin phosphodiesterase gene (SMPD1) coding for ASM. The aim of this study was to evaluate the spectrum of SMPD1 gene mutations in Turkish NPD patients and to study genotype-phenotype associations. We present a molecular analysis of 10 Turkish NPD type A/B patients. Four of the patients had type A and six had type B NPD. All mutant SMPD1 alleles were identified, including 5 different mutations, 1 of which was novel. These mutations included three missense mutations: c.409T>C (p.L137P), c.1262 A>G (p.H421R) and c.1552T>C (p.L549P), a common frameshift mutation in codon 189, identified in three patients, is caused by the deletion of the 567T, introducing a stop codon 65 amino acids downstream (p.P189fsX65), and a novel frameshift mutation c.1755delC (p.P585PfsX24) which was not reported previously.
authors.affiliation: Ege University Faculty of Medicine, Department of Medical Genetics, Izmir, Turkey. aycaaykut@hotmail.com
authors.forename: A
authors.initials: A
authors.lastname: Aykut
authors.forename: E
authors.initials: E
authors.lastname: Karaca
authors.forename: H
authors.initials: H
authors.lastname: Onay
authors.forename: S Kalkan
authors.initials: SK
authors.lastname: Ucar
authors.forename: M
authors.initials: M
authors.lastname: Coker
authors.forename: O
authors.initials: O
authors.lastname: Cogulu
authors.forename: F
authors.initials: F
authors.lastname: Ozkinay
mesh_terms: D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D003062:Codon; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D009542:Niemann-Pick Diseases / Q000175:diagnosis / Q000235:genetics*; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*; D014421:Turkey
chemical_list: D003062:Codon; C543066:SMPD1 protein, human; D013108:Sphingomyelin Phosphodiesterase
keywords: ASM; HDL; MALDI-MS; NPD; Niemann–Pick disease; Novel mutation; PCR; SMPD1; SMPD1 gene; Turkish population; high density lipoprotein; matrix-assisted laser desorption/ionization (MALDI) mass spectrometry; polymerase chain reaction; sphingomyelin phosphodiesterase; sphingomyelin phosphodiesterase gene