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Int. J. Mol. Sci. 2015, 16(4), 6668-6676; doi:10.3390/ijms16046668

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)

1
Department of Biology, Science and Research Branch, Islamic Azad University, Kurdistan 6614996164, Iran
2
Department of Pharmacy, Faculty of Medicine, University of Malaya (UM), Kuala Lumpur 50603, Malaysia
3
Department of Biology, Sanandaj Branch, Islamic Azad University, Kurdistan 6616935391, Iran
4
Medical Genetics Department, Special Medical Center, Tehran 1599666615, Iran
5
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20057, USA
6
Department of Animal Science, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang 43400, Malaysia
7
Medical Genetics Department, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran 1497716316, Iran
*
Author to whom correspondence should be addressed.
Academic Editor: Stephen Bustin
Received: 21 October 2014 / Revised: 15 December 2014 / Accepted: 5 January 2015 / Published: 24 March 2015
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
View Full-Text   |   Download PDF [948 KB, uploaded 24 March 2015]   |  

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. 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. View Full-Text
Keywords: types A and B niemann-pick disease (NPD); sphingomyelin phosphodiesterase 1 (SMPD1) gene; acid sphingomyelinase (ASM); p.G508R; p.N385K and p.V36A; c.1033–1034insT and c.1417–1418delCT types A and B niemann-pick disease (NPD); sphingomyelin phosphodiesterase 1 (SMPD1) gene; acid sphingomyelinase (ASM); p.G508R; p.N385K and p.V36A; c.1033–1034insT and c.1417–1418delCT
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Manshadi, M.D.; Kamalidehghan, B.; Keshavarzi, F.; Aryani, O.; Dadgar, S.; Arastehkani, A.; Tondar, M.; Ahmadipour, F.; Meng, G.Y.; Houshmand, M. 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). Int. J. Mol. Sci. 2015, 16, 6668-6676.

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