AR DC and Mutations in Other Components

In addition to the X-linked recessive and autosomal-dominant forms, a significant fraction of DC families shows an autosomal-recessive form of inheritance. In fact, from the DC Registry of 228 families (Vulliamy et al. 2006), 8% DC patients were observed to fall within this group. Sporadic cases can also be seen, which means only one family member carries a mutation and presents the disease. Efforts have been made to survey mutations in N0P10, NHP2, and GAR1, which are associated with dyskerin and are therefore possible candidates responsible for the autosomal-recessive subtype of this disease (Marrone and Mason 2003, Yamaguchi et al. 2005). So far no diseases causing mutations have been identified. Studies on the archaeal homologs of the four core proteins (Cbf5, Nop10, L7Ae, and Gar1) revealed that Cbf5 independently interacts with the H/ACA RNA, Nop10, and Gar1, while L7Ae did not directly bind with other proteins without mediation of RNA (Baker et al. 2005, Charpentier et al. 2005). Cbf5 associates with the lower stem and ACA motif of RNA via the PUA domain, and the RNA upper stem binds to the structure formed by L7Ae, Nop10, and Cbf5 (Li and Ye 2006). Mutations in the core proteins might affect the association with RNA and the structure and function of the telomerase nucleo-protein complex.

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