Germline thymidylate synthase deficiency impacts nucleotide metabolism and causes dyskeratosis congenita.

ABSTRACT: Dyskeratosis congenita (DC) is an inherited bone-marrow-failure disorder characterized by a triad of mucocutaneous features that include abnormal skin pigmentation, nail dystrophy, and oral leucoplakia. Despite the identification of several genetic variants that cause DC, a significant proportion of probands remain without a molecular diagnosis. In a cohort of eight independent DC-affected families, we have identified a remarkable series of heterozygous germline variants in the gene encoding thymidylate synthase (TYMS). Although the inheritance appeared to be autosomal recessive, one parent in each family had a wild-type TYMS coding sequence. Targeted genomic sequencing identified a specific haplotype and rare variants in the naturally occurring TYMS antisense regulator ENOSF1 (enolase sup

SUBMITTER: Tummala H 

PROVIDER: S-EPMC9388389 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature