Expanding the understanding of telomere biology disorder with reports from two families harboring variants in ZCCHC8 and TERC

In this report, we present two families, one with a pathogenic variant in ZCCHC8 and another with a novel variant in TERC. In the literature, only one family has previously been reported with a ZCCHC8 variant and TBD symptoms. This family had multiple occurrences of pulmonary fibrosis and one case of bone marrow failure. In this paper, we present a second family with the same ZCCHC8 variant (p.Pro186Leu) and symptoms of TBD including pulmonary fibrosis, hematological disease, and elevated liver enzymes. The suspicion of TBD was confirmed with the measurement of short telomeres in the proband. In another family, we report a novel likely pathogenic variant in TERC. Our comprehensive description encompasses hematological manifestations, as well as pulmonary and hepatic fibrosis. Notably, there are no other reports which associate this variant to disease. The families expand our understanding of the clinical implications and genetic causes of TBD.PMID:38606545 | DOI:10.1111/cge.14534

Source: Clinical Genetics - April 12, 2024 Category: Genetics & Stem Cells Authors: Nikolaj Juul Nitschke Anne Marie Jelsig Charlotte Lautrup Malene Lundsgaard Marianne Tang Severinsen Jack Bernard Cowland Lisa Leth Maroun Mette Klarskov Andersen Kirsten Gr ønbæk Source Type: research