端粒生物学障碍(TBD)可以出现广泛的症状,从严重的先天性畸形到成年后的孤立器官功能障碍。考虑到各代人的症状和发病年龄的实质性差异,诊断TBD可能具有挑战性。在这份报告中,我们展示了两个家庭,一种在ZCCHC8中具有致病变体,另一种在TERC中具有新变体。在文学中,以前只有一个家族有ZCCHC8变体和TBD症状。该家庭多次发生肺纤维化和1例骨髓衰竭。在本文中,我们提出了具有相同ZCCHC8变体的第二个家族(p。Pro186Leu)和TBD的症状,包括肺纤维化,血液病,和肝酶升高。通过测量先证者中的短端粒,证实了对TBD的怀疑。在另一个家庭,我们报道了TERC中一种新的可能致病变异。我们的全面描述包括血液学表现,以及肺和肝纤维化。值得注意的是,没有其他报告将这种变异与疾病联系起来。这些家庭扩大了我们对TBD的临床意义和遗传原因的理解。
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.