Exome sequencing reveals novel rare variants in Iranian familial multiple sclerosis: The importance of POLD2 in the disease pathogenesis.
Genomics
; 113(4): 2645-2655, 2021 07.
Article
en En
| MEDLINE
| ID: mdl-34116171
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Exoma
/
Esclerosis Múltiple
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
País/Región como asunto:
Asia
Idioma:
En
Revista:
Genomics
Asunto de la revista:
GENETICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Irán