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British Journal of Haematology Mar 2024By whole exome sequencing, we identified a homozygous c.2086 C→T (p.R696C) TERT mutation in patients who present with a spectrum of variable bone marrow failure (BMF),...
By whole exome sequencing, we identified a homozygous c.2086 C→T (p.R696C) TERT mutation in patients who present with a spectrum of variable bone marrow failure (BMF), raccoon eyes, dystrophic nails, rib anomalies, fragility fractures (FFs), high IgE level, extremely short telomere lengths (TLs), and skewed numbers of cytotoxic T cells with B and NK cytopenia. Haploinsufficiency in the other family members resulted in short TL and osteopenia. These patients also had the lowest bone mineral density Z-score compared to other BMF-patients. Danazol/zoledronic acid improved the outcomes of BMF and FFs. This causative TERT variant has been observed in one family afflicted with dyskeratosis congenita (DC), and thus, we also define a second report and new phenotype related to the variant which should be suspected in severe cases of DC with co-existent BMF, FFs, high IgE level and rib anomalies.
Topics: Humans; Rib Fractures; Telomere; Pancytopenia; Mutation; Dyskeratosis Congenita; Immunoglobulin E; Telomerase
PubMed: 37926112
DOI: 10.1111/bjh.19176