RNA Analysis Uncovers Pathogenic PARN Variant in Dyskeratosis Congenita.

ABSTRACT: Dyskeratosis congenita (DC) is a rare genetic disorder caused by impaired telomere maintenance, leading to diverse clinical manifestations, including bone marrow failure, mucocutaneous abnormalities, and multi-organ dysfunction. Here, we report a 14-year-old male patient presenting with microcephaly, developmental delay, synostoses, cerebellar hypoplasia with ataxia, and an immunodeficiency condition, but lacking classical DC features such as nail dystrophy and skin hyperpigmentation. WGS revealed two variants in the PARN gene: a known pathogenic missense variant (c.1045C > T, p.Arg349Trp) and a novel intronic variant (c.178-28T > C). Functional RNA analysis demonstrated that the intronic variant disrupts the branch point sequence, leading to exon 4 skipping and nonsense-mediated decay (NM

SUBMITTER: Akimova D 

PROVIDER: S-EPMC12779174 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature