A Novel Pathogenic Variant in RTEL1 Causes Dyskeratosis Congenita/Hoyeraal-Hreidarsson Syndrome: A Report of Two Cases

Background: Telomere biology disorders (TBD) are a spectrum of conditions that result from shortened or dysfunctional telomeres. Dyskeratosis congenita (DC) is the prototypic TBD, classically presenting with leukoplakia, dysplastic nails, and reticular skin pigmentation. Immunologic abnormalities are common, and severe infection may be the presenting sign of DC. RTEL1 gene mutations are known to cause DC and are associated with a severe disease phenotype (Hoyeraal-Hreidarsson syndrome). Observation: In this report, we describe 2 patients with severe immunodeficiency and very early onset inflammatory bowel disease found to have novel homozygous mutations in RTEL1 (c.1670T>C, p.L557P). Conclusion: The clinical presentation of these 2 patients with the same novel mutation suggests this mutation is pathogenic and causative of TBD.