Mert Karakaya, Neda Mazaheri, Ipek Polat, Diana Bharucha-Goebel, Sandra Donkervoort, Reza Maroofian, Gholamreza Shariati, Irmgard Hoelker, Kristin Monaghan, Sara Winchester, Robert Zori, Hamid Galehdari, Carsten G. Bönnemann, Uluc Yis, Brunhilde Wirth
With great interest, we read the article by Ylikallio et al. (2017) presenting the first cases with functional molecular analysis of MCM3AP-related Charcot-Marie-Tooth neuropathy (CMT) and mild intellectual disability. MCM3AP has first been proposed as a candidate disease-causing gene for intellectual disability, polyneuropathy and ptosis (Schuurs-Hoeijmakers et al., 2013). Minichromosome maintenance complex component 3 associated protein (MCM3AP, OMIM 603294) functions as an acetyltransferase that acetylates the replication protein, MCM3, and translocates MCM3 into the nuclei from cytoplasm (Takei et al., 2001). Through the interaction with MCM3, MCM3AP inhibits the cell cycle progression to control the DNA replication occurring only once per cell cycle (Takei et al., 2002). Germinal center-associated nuclear protein (GANP) is an alternatively splice variant of MCM3AP, with a carboxyl-domain that is shared with MCM3AP protein (Abe et al., 2000). In addition to this shared carboxyl-terminal domain, GANP is composed of four more functional domains, FG (phenylalanine-glycine) repeat, DNA primase, Sac3 (suppressor of actin) and CID (Cdc31 interaction domain) (Ylikallio et al., 2017). The Sac3 domain is responsible for exporting mRNAs to the cytoplasm through the nuclear pores (Wickramasinghe et al., 2010). A depletion of GANP blocks mRNA export and leads to accumulation of mRNA in punctate foci within the nucleus (Wickramasinghe et al., 2010). Decreased expression of GANP has been shown to be involved in neoplasms originating in the CNS (Ohta et al., 2009).