RTEL1 gene changes affect dyskeratosis congenita caused by telomerase RNA mutations

A C50>A telomerase RNA template mutation leads to the variant telomeric repeat GTTTAG in individuals with dyskeratosis congenita.

• The mutant telomerase exhibits reduced processivity, indicating impaired function.
• Whole-genome sequencing and long-read telomere sequencing reveal inheritance patterns of mutant telomeric repeats.
• An RTEL1 nonsense mutation is linked to very short telomeres in offspring with wild-type telomerase.
• Co-inheritance of the RTEL1 mutation and TERC r.C50>A mutations correlates with severe early-onset dyskeratosis congenita in some individuals.

Simplified