Department of Pediatric, the First Affiliated Hospital of Xi'an Jiaotong University, Xi 'an 710061, People's Republic of China.
Turk J Pediatr. 2023;65(5):845-852. doi: 10.24953/turkjped.2022.344.
Telomeres inhibit DNA damage response at the ends of the chromosome to suppress cell cycle arrest as well as ensure genome stability. Dyskeratosis congenita (DC), a telomere-related disease, includes the classical triad involving oral leukoplakia, dysplastic nails, and lacy reticular pigment in the neck and/or upper chest. Hoyeraal-Hreidarrson syndrome (HHS), a severe manifestation of DC, frequently occurs during childhood, and patients with HHS often show short-term survival and thus do not exhibit all mucocutaneous manifestations or syndromic features.
We report here a patient with HHS characterized by the probands clinical attributes, such as growth delay, bone marrow failure, microcephaly, defects in body development, and the absence of cerebellar hypoplasia combined with Blakes pouch cyst. By using exome sequencing, novel compound heterozygous mutations (c.1451C > T and c.1266+3del78bp) were detected in the RTEL1 (regulator of telomere elongation helicase 1) gene.
The DNA helicase RTEL1 plays a role in genome stability, DNA replication, telomere maintenance, and genome repair. Terminal restriction fragment length analysis revealed a significantly shorter telomere length of the proband. Our findings provided evidence that compound heterozygous RTEL1 mutations cause HHS.
端粒抑制染色体末端的 DNA 损伤反应，以抑制细胞周期停滞并确保基因组稳定性。先天性角化不良（DC）是一种与端粒相关的疾病，包括涉及口腔白斑、发育不良的指甲和颈部和/或上胸部的网状色素沉着的经典三联征。Hoyeraal-Hreidarrson 综合征（HHS）是 DC 的一种严重表现形式，常在儿童期发生，且 HHS 患者常表现为短期生存，因此不会出现所有黏膜皮肤表现或综合征特征。
我们在此报告一例 HHS 患者，其特征为先证者的临床特征，如生长迟缓、骨髓衰竭、小头畸形、身体发育缺陷和无小脑发育不良，同时伴有 Blake`s 囊囊肿。通过外显子组测序，在 RTEL1（端粒延长螺旋酶 1 的调节剂）基因中检测到新型复合杂合突变（c.1451C > T 和 c.1266+3del78bp）。
DNA 解旋酶 RTEL1 参与基因组稳定性、DNA 复制、端粒维持和基因组修复。末端限制性片段长度分析显示先证者的端粒长度明显缩短。我们的研究结果提供了证据，表明 RTEL1 复合杂合突变导致 HHS。
