Monoallelic PARN mutation presenting as pancytopenia, hepatic fibrosis and idiopathic pulmonary fibrosis

A woman in her late 20s presented with a 5-year history of progressive fatigue and generalised weakness. Examination revealed signs of premature ageing, anaemia, neuropathy and hepatosplenomegaly.Investigations showed pancytopenia, dimorphic anaemia, severe vitamin B12 deficiency, hepatic fibrosis and pulmonary fibrosis. Despite correction of nutritional deficiencies, the constellation of cytopenia, premature greying, osteoporosis, hepatic and pulmonary fibrosis raised suspicion of a genetic disorder. Clinical exome sequencing identified a monoallelic PARN missense variant (c.613T>C; p.Cys205Arg), classified as a Variant of Uncertain Significance. Germline pathogenic variants in PARN have been associated with dyskeratosis congenita, autosomal recessive 6 (DKCB6) and with telomere-related pulmonary fibrosis and/or bone marrow failure 4. The clinical–genetic correlation in this case supported a diagnosis of a telomere biology disorder (TBD). This case highlights the importance of considering TBDs in young adults with unexplained multisystem disease, even when classical mucocutaneous features are absent. Early recognition is crucial for guiding genetic counselling, surveillance and consideration of bone marrow transplantation in progressive cases.