Biallelic RTEL1 mutations were observed in a further six index cases, all of whom had a similar clinical phenotype, resulting in the identification of one homozygous and eight heterozygous mutations, of which six were missense, two affected the donor splice site, and one was a stop-gain mutation (Table 1, Figures 1B and 1C, and Table S3). The missense mutations identified occurred at residues that are generally highly conserved, and five of them aligned across mouse, chicken, and fruit fly proteins (Figure 1B). c.2941C>T (p.Arg981Trp) was recurrent—it was seen in three families (DCR families 237, 303, and 333). In total, 11 different RTEL1 mutations were identified in ten cases from seven families, and all of them segregated with disease as an autosomal-recessive trait (Figure 1A).