Exome sequencing reveals novel rare variants in Iranian familial multiple sclerosis : The importance of POLD2 in the disease pathogenesis
Copyright © 2021 Elsevier Inc. All rights reserved..
The prevalence of familial multiple sclerosis (FMS) is increasing worldwide which endorses the heritability of the disease. Given that many genome variations are ethnicity-specific and consanguineous marriage could affect genetic diseases, hereditary disease gene analysis among FMS patients from Iran, a country with high rates of parental consanguinity, could be highly effective in finding mutations underlying disease pathogenesis. To examine rare genetic mutations, we selected three Iranian FMS cases with ≥3 MS patients in more than one generation and performed whole exome sequencing. We identified a homozygous rare missense variant in POLD2 (p. Arg141Cys; rs372336011). Molecular dynamics analysis showed reduced polar dehydration energy and conformational changes in POLD2 mutant. Further, we found a heterozygote rare missense variant in NBFP1 (p. Gly487Asp; rs778806175). Our study revealed the possible role of novel rare variants in FMS. Molecular dynamic simulation provided the initial evidence of the structural changes behind POLD2 mutant.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:113 |
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| Enthalten in: |
Genomics - 113(2021), 4 vom: 15. Juli, Seite 2645-2655 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Salehi, Zahra [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 31.03.2022 Date Revised 07.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ygeno.2021.06.008 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM326641173 |
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| 100 | 1 | |a Salehi, Zahra |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Exome sequencing reveals novel rare variants in Iranian familial multiple sclerosis |b The importance of POLD2 in the disease pathogenesis |
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| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Inc. All rights reserved. | ||
| 520 | |a The prevalence of familial multiple sclerosis (FMS) is increasing worldwide which endorses the heritability of the disease. Given that many genome variations are ethnicity-specific and consanguineous marriage could affect genetic diseases, hereditary disease gene analysis among FMS patients from Iran, a country with high rates of parental consanguinity, could be highly effective in finding mutations underlying disease pathogenesis. To examine rare genetic mutations, we selected three Iranian FMS cases with ≥3 MS patients in more than one generation and performed whole exome sequencing. We identified a homozygous rare missense variant in POLD2 (p. Arg141Cys; rs372336011). Molecular dynamics analysis showed reduced polar dehydration energy and conformational changes in POLD2 mutant. Further, we found a heterozygote rare missense variant in NBFP1 (p. Gly487Asp; rs778806175). Our study revealed the possible role of novel rare variants in FMS. Molecular dynamic simulation provided the initial evidence of the structural changes behind POLD2 mutant | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Consanguineous marriage | |
| 650 | 4 | |a Familial multiple sclerosis | |
| 650 | 4 | |a Molecular dynamics | |
| 650 | 4 | |a Rare variants | |
| 650 | 4 | |a Whole-exome sequencing | |
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| 700 | 1 | |a Keramatipour, Mohammad |e verfasserin |4 aut | |
| 700 | 1 | |a Talebi, Saeed |e verfasserin |4 aut | |
| 700 | 1 | |a Arab, Seyed Shahriar |e verfasserin |4 aut | |
| 700 | 1 | |a Naser Moghadasi, Abdorreza |e verfasserin |4 aut | |
| 700 | 1 | |a Sahraian, Mohammad Ali |e verfasserin |4 aut | |
| 700 | 1 | |a Izad, Maryam |e verfasserin |4 aut | |
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