In patients with Hoyeraal–Hreidarsson syndrome (a severe variant of dyskeratosis congenita), mutation affects the RTEL1 C4C4 metal-binding motif [150], so that RTEL1 no longer binds to TRF2, and this RTEL1 variant fails to rescue the telomere loss and the telomere circles induced by RTEL1 deletion [70]. The gene discussed is RTEL1; the disease is dyskeratosis congenita.