Exome Sequencing Reveals Novel Rare Variants in Iranian Familial Multiple Sclerosis: The Importance of Pold2 in the Disease Pathogenesis Publisher Pubmed



Salehi Z¹ ; Keramatipour M² ; Talebi S^{3, 4} ; Arab SS⁵ ; Naser Moghadasi A⁶ ; Sahraian MA⁶ ; Izad M^{1, 6}
Source: Genomics Published:2021

Abstract

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. © 2021 Elsevier Inc.