{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:03:30Z","timestamp":1791194610103,"version":"4.1.0"},"reference-count":20,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T00:00:00Z","timestamp":1427155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u20131034insT mutation. One patient was homozygous for the c.573delT mutation, and 1 patient was homozygous for the c.1417\u20131418delCT 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. Conclusion: 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.<\/jats:p>","DOI":"10.3390\/ijms16046668","type":"journal-article","created":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T13:07:25Z","timestamp":1427202445000},"page":"6668-6676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Four Novel p.N385K, p.V36A, c.1033\u20131034insT and  c.1417\u20131418delCT Mutations in the Sphingomyelin Phosphodiesterase 1 (SMPD1) Gene in Patients with Types A and B Niemann-Pick Disease (NPD)"],"prefix":"10.3390","volume":"16","author":[{"given":"Masoumeh","family":"Manshadi","sequence":"first","affiliation":[{"name":"Department of Biology, Science and Research Branch, Islamic Azad University,  Kurdistan 6614996164, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behnam","family":"Kamalidehghan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Malaya (UM), Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Keshavarzi","sequence":"additional","affiliation":[{"name":"Department of Biology, Sanandaj Branch, Islamic Azad University, Kurdistan 6616935391, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omid","family":"Aryani","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Special Medical Center, Tehran 1599666615, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Dadgar","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Special Medical Center, Tehran 1599666615, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahoora","family":"Arastehkani","sequence":"additional","affiliation":[{"name":"Department of Biology, Science and Research Branch, Islamic Azad University,  Kurdistan 6614996164, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi","family":"Tondar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular & Cellular Biology, Georgetown University,  Washington, DC 20057, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Ahmadipour","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Malaya (UM), Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goh","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Faculty of Veterinary Medicine, Universiti Putra Malaysia,  Serdang 43400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massoud","family":"Houshmand","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Special Medical Center, Tehran 1599666615, Iran"},{"name":"Medical Genetics Department, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran 1497716316, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jpeds.2004.02.048","article-title":"Lipid abnormalities in children with types A and B Niemann Pick disease","volume":"145","author":"McGovern","year":"2004","journal-title":"J. Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1212\/01.wnl.0000194208.08904.0c","article-title":"Natural history of Type A Niemann-Pick disease Possible endpoints for therapeutic trials","volume":"66","author":"McGovern","year":"2006","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/s10545-007-0632-9","article-title":"The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease","volume":"30","author":"Schuchman","year":"2007","journal-title":"J. Inherit. Metab. Dis"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e672","DOI":"10.1542\/peds.2004-0887","article-title":"The natural history of type B Niemann-Pick disease: results from a 10-year longitudinal study","volume":"114","author":"Wasserstein","year":"2004","journal-title":"Pediatrics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"316","DOI":"10.2119\/molmed.2010.00017","article-title":"Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease","volume":"16","author":"Desnick","year":"2010","journal-title":"Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/j.1440-1843.2008.01352.x","article-title":"Lung cyst: An unusual manifestation of Niemann-Pick disease","volume":"14","author":"Baldi","year":"2009","journal-title":"Respirology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1542\/peds.2007-3016","article-title":"A prospective, cross-sectional survey study of the natural history of Niemann-Pick type B disease","volume":"122","author":"McGovern","year":"2009","journal-title":"Pediatrics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5440","DOI":"10.1016\/S0021-9258(17)37705-0","article-title":"Processing of human acid sphingomyelinase in normal and I-cell fibroblasts","volume":"267","author":"Hurwitz","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_9","unstructured":"McGovern, M.M., and Schuchman, E.H. Acid sphingomyelinase deficiency, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1370\/."},{"key":"ref_10","first-page":"S48","article-title":"The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease","volume":"47","author":"Schuchman","year":"2008","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1073\/pnas.55.2.366","article-title":"The metabolism of sphingomyelin II.Evidence of an enzymatic deficiency in Niemann-Pick diseae","volume":"55","author":"Brady","year":"1966","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S0022-2275(20)40138-5","article-title":"Sphingomyelinase in normal human spleens and in spleens from subjects with Niemann-Pick disease","volume":"8","author":"Schneider","year":"1967","journal-title":"J. Lipid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nature08710","article-title":"Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology","volume":"463","author":"Kirkegaard","year":"2010","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/BF00291589","article-title":"Somatic cell hybridisation studies showing different gene mutations in Niemann-Pick variants","volume":"54","author":"Besley","year":"1980","journal-title":"Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/humu.9353","article-title":"Functional in vitro characterization of 14 SMPD1 mutations identified in Italian patients affected by Niemann Pick Type B disease","volume":"26","author":"Dardis","year":"2005","journal-title":"Hum. Mutat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1182\/blood.V80.8.2081.2081","article-title":"Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients","volume":"80","author":"Levran","year":"1992","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ymgme.2009.01.008","article-title":"Pulmonary delivery of recombinant acid sphingomyelinase improves clearance of lysosomal sphingomyelin from the lungs of a murine model of Niemann-Pick disease","volume":"97","author":"Ziegler","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1445-5994.2005.01013.x","article-title":"Clinical findings in Niemann-Pick disease type B","volume":"36","author":"Harzer","year":"2006","journal-title":"Int. Med. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1086\/345074","article-title":"The demographics and distribution of type B Niemann-Pick disease: Novel mutations lead to new genotype\/phenotype correlations","volume":"71","author":"Simonaro","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/(SICI)1098-1004(1998)12:2<136::AID-HUMU12>3.0.CO;2-Y","article-title":"Niemann Pick disease type A in Israeli Arabs: 677delT, a common novel single mutation","volume":"12","author":"Gluck","year":"1999","journal-title":"Hum. 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