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DCDC2 Mutations Cause Neonatal Sclerosing Cholangitis
Author(s) -
Girard Muriel,
Bizet Albane A.,
Lachaux Alain,
Gonzales Emmanuel,
Filhol Emilie,
CollardeauFrachon Sophie,
Jeanpierre Cécile,
Henry Charline,
Fabre Monique,
Viremouneix Loic,
Galmiche Louise,
Debray Dominique,
BoleFeysot Christine,
Nitschke Patrick,
Pariente Danièle,
Guettier Catherine,
Lyonnet Stanislas,
Heidet Laurence,
Bertholet Aurelia,
Jacquemin Emmanuel,
HenrionCaude Alexandra,
Saunier Sophie
Publication year - 2016
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23031
Subject(s) - ciliogenesis , ciliopathy , biology , missense mutation , doublecortin , cilium , motile cilium , genetics , mutation , cancer research , gene , phenotype , neuroscience , hippocampal formation , dentate gyrus
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. This is the first report of DCDC2 mutations in NSC. This data expands the molecular spectrum of NSC, that can be considered as a ciliopathy and also expands the clinical spectrum of the DCDC2 mutations, previously reported in dyslexia, deafness, and nephronophtisis.