The alterations caused by the mutations identified in this study were spread throughout RTEL1 (Figure 1C), and four were within the RAD3-related helicase domain. Helicases are a group of proteins that function by using ATP hydrolysis to catalyze the unwinding of polynucleic-acid structures and are involved in DNA repair, replication, recombination, chromosomal segregation, and telomere maintenance.20 They can be classified into several families, some of which are associated with human disease. One such family is the RECQ helicase family; alterations in WRN, BLM, and RECQL4 cause Werner syndrome (MIM 604611), Bloom syndrome (MIM 604610), and Rothmund-Thomson syndrome (MIM 603780),21 respectively. The most recently identified helicase family with telomere effects is the FANCJ family, which has several members, including BRIP1 (FANCJ) and RTEL1. BRIP1 is associated with Fanconi anemia (FA [MIM 227650]),22 a disorder characterized by DNA repair and/or homologous recombination defects, and RTEL1 (shown in this study) is associated with HHS. These diseases have some overlapping features, but there are also clear differences. None of the RECQ-associated diseases have global BM failure, but there is an increased risk of cancers, whereas both FA and DC are characterized by BM failure. Peripheral-blood lymphocytes from several individuals with biallelic RTEL1 mutations were tested for chromosomal breakage after exposure to DNA cross-linking agents in the standard FA test (Table 1), but unlike lymphocytes from individuals with FA, they had no increased chromosomal breakage. This demonstrates that lymphocytes with biallelic RTEL1 mutations do not exhibit the same cellular defects as lymphocytes from individuals with FA, suggesting that cells with biallelic RTEL1 mutations do not have significant defects in DNA repair and/or homologous recombination.