Centre for Paediatrics, Barts, UK.
Haematologica. 2013 Mar;98(3):334-8. doi: 10.3324/haematol.2012.071068. Epub 2012 Aug 16.
Dyskeratosis congenita and its variants have overlapping phenotypes with many disorders including Coats plus, and their underlying pathology is thought to be one of defective telomere maintenance. Recently, biallelic CTC1 mutations have been described in patients with syndromes overlapping Coats plus. CTC1, STN1 and TEN1 are part of the telomere-capping complex involved in maintaining telomeric structural integrity. Based on phenotypic overlap we screened 73 genetically uncharacterized patients with dyskeratosis congenita and related bone marrow failure syndromes for mutations in this complex. Biallelic CTC1 mutations were identified in 6 patients but none in either STN1 or TEN1. We have expanded the phenotypic spectrum associated with CTC1 mutations and report that intracranial and retinal abnormalities are not a defining feature, as well as showing that the effect of these mutations on telomere length is variable. The study also demonstrates the lack of disease-causing mutations in other components of the telomere-capping complex.
先天性角化不良及其变体与包括 Coats 病在内的许多疾病具有重叠的表型，其潜在病理学被认为是端粒维持缺陷之一。最近，在与 Coats 病重叠的综合征患者中描述了双等位基因 CTC1 突变。CTC1、STN1 和 TEN1 是参与维持端粒结构完整性的端粒加帽复合物的一部分。基于表型重叠，我们对 73 名患有先天性角化不良和相关骨髓衰竭综合征的遗传特征未知的患者进行了该复合物突变的筛查。在 6 名患者中发现了双等位基因 CTC1 突变，但在 STN1 或 TEN1 中均未发现。我们扩展了与 CTC1 突变相关的表型谱，并报告颅内和视网膜异常不是其特征性表现，同时表明这些突变对端粒长度的影响是可变的。该研究还表明端粒加帽复合物的其他成分中不存在致病突变。
