Background. 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.

Case. 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.

Conclusions. 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.

Keywords: Blake`s pouch cyst, Hoyeraal-Hreidarsson syndrome, dyskeratosis congenita, telomere length