Segregation of RTEL1 Mutations in HHS-Affected Families and the Location of RTEL1 Alterations in the Different Protein Domains
(A) Segregation of RTEL1 mutations causing HHS. Shown are seven families in which RTEL1 mutations segregate as an autosomal-recessive trait. Where available, the genotype of each individual is shown as a plus sign for the wild-type allele and as a minus sign for the mutated allele. The asterisk indicates that the mutation appears to have arisen de novo.
(B) Conservation of altered RTEL1 amino acids. Blocks of amino acid alignment were generated with ClustalW and show the degree of conservation of the altered amino acid residues in RTEL1. Sequences are as follows: human, H. sapiens (RTEL1 [RefSeq NP_116575.3]); mouse, M. musculus (RTEL1 [RefSeq NP_001001882.3]); chicken, G. gallus (RTEL1 [RefSeq XP_417435.3]); and fruit fly, D. melanogaster (RTEL1 [RefSeq NP_572254.1]). Asterisks indicate positions that have a single fully conserved residue, colons indicate conservation between groups of strongly similar properties, and periods indicate conservation between groups of weakly similar properties.
(C) Conserved functional domains predicted in the RTEL1 amino acid sequence show the relative positions of the alterations caused by the mutations observed in our subject group. Domains are as follows: I–VI, helicase domains; PIP, proliferating cell nuclear antigen (PCNA)-interacting protein domain; green bar, iron-sulfur domain; purple bar, DEXDc2-DEAD-like helicase superfamily domain; brown bar, DEAH box; orange bar, helicase C-terminal domain; and blue bar, helicase, superfamily 1 and 2, ATP-binding domain, DinG/Rad3-type. The hatched C terminus is from isoform uc021wge.1.