ERCC2 mutations in two siblings with a severe trichothiodystrophy phenotype

Trichothiodystrophy (TTD) describes a group of rare genetic disorders of DNA repair, characterized by sulphur-deficient hair, skin anomalies and systemic complications like preterm delivery, neurological impairment, haematological and ophthalmological abnormalities and life-threatening infections.

The aim of this case report was to investigate the contribution of the gene mutation to the phenotype.

We describe the clinical and molecular characteristics of a family with two TTD-affected siblings who died before the age of 2 years.

The causal mutated gene is the ERCC2 gene, and one of the identified mutations is the c.2164C>T (p.Arg722Trp) variant. The association of this mutation with a severe TTD phenotype was suggested earlier in literature, and the present family adds further evidence to this hypothesis.

Accurate identification of the underlying genetic defect can guide the clinical follow-up and counselling of patients and their families.