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)
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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2015-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1422-0067/16/4/6668 |
| _version_ | 1811299772458336256 |
|---|---|
| author | Masoumeh Dehghan Manshadi Behnam Kamalidehghan Fatemeh Keshavarzi Omid Aryani Sepideh Dadgar Ahoora Arastehkani Mahdi Tondar Fatemeh Ahmadipour Goh Yong Meng Massoud Houshmand |
| author_facet | Masoumeh Dehghan Manshadi Behnam Kamalidehghan Fatemeh Keshavarzi Omid Aryani Sepideh Dadgar Ahoora Arastehkani Mahdi Tondar Fatemeh Ahmadipour Goh Yong Meng Massoud Houshmand |
| author_sort | Masoumeh Dehghan Manshadi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T06:41:41Z |
| format | Article |
| id | doaj.art-055f2e6518b3495394e118d057421ae4 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T06:41:41Z |
| publishDate | 2015-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-055f2e6518b3495394e118d057421ae42022-12-22T02:57:43ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-03-011646668667610.3390/ijms16046668ijms16046668Four 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)Masoumeh Dehghan Manshadi0Behnam Kamalidehghan1Fatemeh Keshavarzi2Omid Aryani3Sepideh Dadgar4Ahoora Arastehkani5Mahdi Tondar6Fatemeh Ahmadipour7Goh Yong Meng8Massoud Houshmand9Department of Biology, Science and Research Branch, Islamic Azad University, Kurdistan 6614996164, IranDepartment of Pharmacy, Faculty of Medicine, University of Malaya (UM), Kuala Lumpur 50603, MalaysiaDepartment of Biology, Sanandaj Branch, Islamic Azad University, Kurdistan 6616935391, IranMedical Genetics Department, Special Medical Center, Tehran 1599666615, IranMedical Genetics Department, Special Medical Center, Tehran 1599666615, IranDepartment of Biology, Science and Research Branch, Islamic Azad University, Kurdistan 6614996164, IranDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20057, USADepartment of Pharmacy, Faculty of Medicine, University of Malaya (UM), Kuala Lumpur 50603, MalaysiaDepartment of Animal Science, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang 43400, MalaysiaMedical Genetics Department, Special Medical Center, Tehran 1599666615, IranBackground: 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.http://www.mdpi.com/1422-0067/16/4/6668types A and B niemann-pick disease (NPD)sphingomyelin phosphodiesterase 1 (SMPD1) geneacid sphingomyelinase (ASM)p.G508Rp.N385K and p.V36Ac.1033–1034insT and c.1417–1418delCT |
| spellingShingle | Masoumeh Dehghan Manshadi Behnam Kamalidehghan Fatemeh Keshavarzi Omid Aryani Sepideh Dadgar Ahoora Arastehkani Mahdi Tondar Fatemeh Ahmadipour Goh Yong Meng Massoud Houshmand 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) International Journal of Molecular Sciences 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 |
| 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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 |
| topic | 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 |
| url | http://www.mdpi.com/1422-0067/16/4/6668 |
| work_keys_str_mv | AT masoumehdehghanmanshadi fournovelpn385kpv36ac10331034instandc14171418delctmutationsinthesphingomyelinphosphodiesterase1smpd1geneinpatientswithtypesaandbniemannpickdiseasenpd AT behnamkamalidehghan fournovelpn385kpv36ac10331034instandc14171418delctmutationsinthesphingomyelinphosphodiesterase1smpd1geneinpatientswithtypesaandbniemannpickdiseasenpd AT fatemehkeshavarzi fournovelpn385kpv36ac10331034instandc14171418delctmutationsinthesphingomyelinphosphodiesterase1smpd1geneinpatientswithtypesaandbniemannpickdiseasenpd AT omidaryani fournovelpn385kpv36ac10331034instandc14171418delctmutationsinthesphingomyelinphosphodiesterase1smpd1geneinpatientswithtypesaandbniemannpickdiseasenpd AT sepidehdadgar fournovelpn385kpv36ac10331034instandc14171418delctmutationsinthesphingomyelinphosphodiesterase1smpd1geneinpatientswithtypesaandbniemannpickdiseasenpd AT ahooraarastehkani fournovelpn385kpv36ac10331034instandc14171418delctmutationsinthesphingomyelinphosphodiesterase1smpd1geneinpatientswithtypesaandbniemannpickdiseasenpd AT mahditondar fournovelpn385kpv36ac10331034instandc14171418delctmutationsinthesphingomyelinphosphodiesterase1smpd1geneinpatientswithtypesaandbniemannpickdiseasenpd AT fatemehahmadipour fournovelpn385kpv36ac10331034instandc14171418delctmutationsinthesphingomyelinphosphodiesterase1smpd1geneinpatientswithtypesaandbniemannpickdiseasenpd AT gohyongmeng fournovelpn385kpv36ac10331034instandc14171418delctmutationsinthesphingomyelinphosphodiesterase1smpd1geneinpatientswithtypesaandbniemannpickdiseasenpd AT massoudhoushmand fournovelpn385kpv36ac10331034instandc14171418delctmutationsinthesphingomyelinphosphodiesterase1smpd1geneinpatientswithtypesaandbniemannpickdiseasenpd |