背景: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。先天性角化病(DC),端粒相关疾病,包括涉及口腔白斑的经典三合会,发育不良的指甲,颈部和/或上胸部的花边网状色素。Hoyeraal-Hreidarrson综合征(HHS),DC的严重表现,经常发生在童年,HHS患者通常表现出短期生存,因此并不表现出所有的粘膜皮肤表现或综合征特征。
方法:我们在此报告了一名以先证者的临床特征为特征的HHS患者,比如生长延迟,骨髓衰竭,小头畸形,身体发育缺陷,没有小脑发育不全合并Blake's囊囊肿.通过使用外显子组测序,在RTEL1(端粒延伸解旋酶1的调节因子)基因中检测到新的复合杂合突变(c.14511C>T和c.12663del78bp)。
结论:DNA解旋酶RTEL1在基因组稳定性中起作用,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子的端粒长度明显较短。我们的发现提供了复合杂合RTEL1突变导致HHS的证据。
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 proband`s clinical attributes, such as growth delay, bone marrow failure, microcephaly, defects in body development, and the absence of cerebellar hypoplasia combined with Blake`s 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.