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

Authors :
Nitschke, Nikolaj Juul
Jelsig, Anne Marie
Lautrup, Charlotte
Lundsgaard, Malene
Severinsen, Marianne Tang
Cowland, Jack Bernard
Maroun, Lisa Leth
Andersen, Mette Klarskov
Grønbæk, Kirsten
Source :
Clinical Genetics. Aug2024, Vol. 106 Issue 2, p187-192. 6p.
Publication Year :
2024

Abstract

Telomere biology disorder (TBD) can present within a wide spectrum of symptoms ranging from severe congenital malformations to isolated organ dysfunction in adulthood. Diagnosing TBD can be challenging given the substantial variation in symptoms and age of onset across generations. 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00099163
Volume :
106
Issue :
2
Database :
Academic Search Index
Journal :
Clinical Genetics
Publication Type :
Academic Journal
Accession number :
178178483
Full Text :
https://doi.org/10.1111/cge.14534