Biallelic TERT variant leads to Hoyeraal-Hreidarsson syndrome with additional dyskeratosis congenita findings

Abstract

Short telomere syndromes constitute a heterogeneous group of clinical conditions characterized by short telomeres and impaired telomerase activity due to pathogenic variants in the essential telomerase components. Dyskeratosis congenita (DC) is a rare, multisystemic telomere biology disorder characterized by abnormal skin pigmentation, oral leukoplakia and nail dysplasia along with various somatic findings. Hoyeraal-Hreidarsson syndrome (HHS) is generally an autosomal recessively inherited subgroup showing growth retardation, microcephaly, cerebellar hypoplasia and severe immunodeficiency. We here report on a consanguineous family from Turkey, in which a missense variant in the reverse transcriptase domain of the TERT gene segregated with short telomere lengths and was associated with full-blown short telomere syndrome phenotype in the index; and heterogeneous adult-onset manifestations in heterozygous individuals.