title: Four novel p.N385K, p.V36A, c.1033-1034insT and c.1417-1418delCT mutations in the sphingomyelin Phosphodiesterase 1 (SMPD1) gene in patients with types A and B Niemann-Pick disease (NPD).
abstract: BACKGROUND
  Types A and B Niemann-Pick disease (NPD) are autosomal-recessive lysosomal storage disorders caused by the deficient activity of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene.
  
  
  METHODS
  In order to determine the prevalence and distribution of SMPD1 gene mutations, the genomic DNA of 15 unrelated Iranian patients with types A and B NPD was examined using PCR, DNA sequencing and bioinformatics analysis.
  
  
  RESULTS
  Of 8 patients with the p.G508R mutation, 5 patients were homozygous, while the other 3 were heterozygous. One patient was heterozygous for both the p.N385K and p.G508R mutations. Another patient was heterozygous for both the p.A487V and p.G508R mutations. Two patients (one homozygous and one heterozygous) showed the p.V36A mutation. One patient was homozygous for the c.1033-1034insT mutation. One patient was homozygous for the c.573delT mutation, and 1 patient was homozygous for the c.1417-1418delCT mutation. Additionally, bioinformatics analysis indicated that two new p.V36A and p.N385K mutations decreased the acid sphingomyelinase (ASM) protein stability, which might be evidence to suggest the pathogenicity of these mutations.
  
  
  CONCLUSIONS
  with detection of these new mutations, the genotypic spectrum of types A and B NPD is extended, facilitating the definition of disease-related mutations. However, more research is essential to confirm the pathogenic effect of these mutations.
authors: Department of Biology, Science and Research Branch, Islamic Azad University, Kurdistan 6614996164, Iran. m_dehghanmanshadi@yahoo.com.
authors: Masoumeh Dehghan
authors: MD
authors: Manshadi
authors: Department of Pharmacy, Faculty of Medicine, University of Malaya (UM), Kuala Lumpur 50603, Malaysia. kamalidehghan.behnam@gmail.com.
authors: Behnam
authors: B
authors: Kamalidehghan
authors: Department of Biology, Sanandaj Branch, Islamic Azad University, Kurdistan 6616935391, Iran. gol.keshavarzi@gmail.com.
authors: Fatemeh
authors: F
authors: Keshavarzi
authors: Medical Genetics Department, Special Medical Center, Tehran 1599666615, Iran. o_aryani@yahoo.com.
authors: Omid
authors: O
authors: Aryani
authors: Medical Genetics Department, Special Medical Center, Tehran 1599666615, Iran. sepideh.dadgar@gmail.com.
authors: Sepideh
authors: S
authors: Dadgar
authors: Department of Biology, Science and Research Branch, Islamic Azad University, Kurdistan 6614996164, Iran. ahoora_mazda_930@yahoo.com.
authors: Ahoora
authors: A
authors: Arastehkani
authors: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20057, USA. mt969@georgetown.edu.
authors: Mahdi
authors: M
authors: Tondar
authors: Department of Pharmacy, Faculty of Medicine, University of Malaya (UM), Kuala Lumpur 50603, Malaysia. ahmadipourf@gmail.com.
authors: Fatemeh
authors: F
authors: Ahmadipour
authors: Department of Animal Science, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang 43400, Malaysia. gohyongmeng@gmail.com.
authors: Goh Yong
authors: GY
authors: Meng
authors: Medical Genetics Department, Special Medical Center, Tehran 1599666615, Iran. massoudh@nigeb.ac.ir.|Medical Genetics Department, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran 1497716316, Iran. massoudh@nigeb.ac.ir.
authors: Massoud
authors: M
authors: Houshmand
mesh_terms: D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D007492:Iran; D009154:Mutation; D052536:Niemann-Pick Disease, Type A / Q000235:genetics*; D052537:Niemann-Pick Disease, Type B / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C543066:SMPD1 protein, human; D013108:Sphingomyelin Phosphodiesterase