PRDX1 gene-related epi-cblC disease is a common type of inborn error of cobalamin metabolism with mono- or bi-allelic MMACHC epimutations.

Fiche publication


Date publication

juillet 2021

Journal

Clinical epigenetics

Auteurs

Membres identifiés du Cancéropôle Est :
Pr GUEANT Jean-Louis, Dr OUSSALAH Abderrahim


Tous les auteurs :
Cavicchi C, Oussalah A, Falliano S, Ferri L, Gozzini A, Gasperini S, Motta S, Rigoldi M, Parenti G, Tummolo A, Meli C, Menni F, Furlan F, Daniotti M, Malvagia S, la Marca G, Chery C, Morange PE, Tregouet D, Donati MA, Guerrini R, Guéant JL, Morrone A

Résumé

The role of epigenetics in inborn errors of metabolism (IEMs) is poorly investigated. Epigenetic changes can contribute to clinical heterogeneity of affected patients but could also be underestimated determining factors in the occurrence of IEMs. An epigenetic cause of IEMs has been recently described for the autosomal recessive methylmalonic aciduria and homocystinuria, cblC type (cblC disease), and it has been named epi-cblC. Epi-cblC has been reported in association with compound heterozygosity for a genetic variant and an epimutation at the MMACHC locus, which is secondary to a splicing variant (c.515-1G > T or c.515-2A > T) at the adjacent PRDX1 gene. Both these variants cause aberrant antisense transcription and cis-hypermethylation of the MMACHC gene promotor with subsequent silencing. Until now, only nine epi-cblC patients have been reported.

Mots clés

CpG island, Epi-cblC, Expanded newborn screening (NBS), Methylmalonic aciduria and homocystinuria, Promoter hypermethylation, Secondary epimutation, cblC disease, cblC type

Référence

Clin Epigenetics. 2021 Jul 2;13(1):137