Predicted amino acid changes and family trees of patients with ERCC6L2 mutations. (A) Graphical representation of ERCC6L2 protein. Functional domains (top part) such as helicase domains are depicted in green, phosphoserines in gray, and DEAH boxes that denote Asp-Glu-Ala-His box in blue. The bottom part shows amino acid alignments using ClustalW, representing conservation among different species. (B) A 3D model of the ERCC6L2 amino acid substitution (yellow part, indicated by an arrow) highlighting the location of this amino acid in a conserved helicase domain. (C) Family trees for the 7 patients with ERCC6L2 biallelic mutations (5 families). Where parental DNA was available and both paternity and maternity were confirmed (family 1 and 6), each parent bore 1 allele. Patients from consanguineous union in families 1 and 2 had homozygous ERCC6L2 mutations. Of note, families 1 and 3 with identical variants were unrelated.