Muriel Girard, Albane A Bizet, Alain Lachaux, Emmanuel Gonzales, Emilie Filhol, Sophie Collardeau-Frachon, Cécile Jeanpierre, Charline Henry, Monique Fabre, Loic Viremouneix, Louise Galmiche, Dominique Debray, Christine Bole-Feysot, Patrick Nitschke, Danièle Pariente, Catherine Guettier, Stanislas Lyonnet, Laurence Heidet, Aurelia Bertholet, Emmanuel Jacquemin, Alexandra Henrion-Caude, Sophie Saunier
Neonatal sclerosing cholangitis (NSC) is a rare biliary disease leading to liver transplantation in childhood. Patients with NSC and ichtyosis have already been identified with a CLDN1 mutation, encoding a tight-junction protein. However, for the majority of patients, the molecular basis of NSC remains unknown. We identified biallelic missense mutations or in-frame deletion in DCDC2 in four affected children. Mutations involve highly conserved amino acids in the doublecortin domains of the protein. In cholangiocytes, DCDC2 protein is normally located in the cytoplasm and cilia, whereas in patients the mutated protein is accumulated in the cytoplasm, absent from cilia, and associated with ciliogenesis defect...
October 2016: Human Mutation