Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance

APL Marsh; D Heron; TJ Edwards; A Quartier; C Galea; C Nava; A Rastetter; ML Moutard; V Anderson; P Bitoun; J Bunt; A Faudet; C Garel; G Gillies; I Gobius; J Guegan; S Heide; B Keren; F Lesne; V Lukic; SA Mandelstam; G McGillivray; A McIlroy; A Méneret; C Mignot; LR Morcom; S Odent; A Paolino; K Pope; F Riant; GA Robinson; M Spencer-Smith; M Srour; SEM Stephenson; R Tankard; O Trouillard; Q Welniarz; A Wood; A Brice; G Rouleau; T Attié-Bitach; MB Delatycki; JL Mandel; DJ Amor; E Roze; A Piton; M Bahlo; T Billette De Villemeur; EH Sherr; RJ Leventer; LJ Richards; PJ Lockhart; C Depienne

Journal article

Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance

APL Marsh, D Heron, TJ Edwards, A Quartier, C Galea, C Nava, A Rastetter, ML Moutard, V Anderson, P Bitoun, J Bunt, A Faudet, C Garel, G Gillies, I Gobius, J Guegan, S Heide, B Keren, F Lesne, V Lukic Show all

Nature Genetics | NATURE PUBLISHING GROUP | Published : 2017

DOI: 10.1038/ng.3794

Abstract

Brain malformations involving the corpus callosum are common in children with developmental disabilities. We identified DCC mutations in four families and five sporadic individuals with isolated agenesis of the corpus callosum (ACC) without intellectual disability. DCC mutations result in variable dominant phenotypes with decreased penetrance, including mirror movements and ACC associated with a favorable developmental prognosis. Possible phenotypic modifiers include the type and location of mutation and the sex of the individual.

University of Melbourne Researchers

Vicki Anderson Author

Sarah Stephenson Author

Martin Delatycki Author

David Amor Author

Grants

Awarded by Seventh Framework Programme

Funding Acknowledgements

We thank the studied families and the Lefroy family for their participation in and support of this study. We thank the DNA and cell bank of the ICM (Paris, France) for DNA extraction, Sinead Eyre (QBI) for study coordination and M. Kean (RCH) and M. Seal (MCRI) for assistance with MRI protocols and scanning. This work was funded in part by National Health and Medical Research Council (NHMRC) Australia Project grants (GNT1059666, GNT631466, GNT1064174, GNT1048849, GNT1104455 and GNT1064174), the Agence Nationale de la Recherche (ANR Blanc CILAXCAL, ANR Blanc HARTaGeNe), Assistance Publique des Hopitaux de Paris (APHP), the 'Programme Hospitalier de Recherche Clinique' (PHRC) ACCREM, and the 'Investissements d'Avenir' programs ANR-10-IAIHU-06 (IHU-A-ICM), ANR-10-LABX-0030-INRT and ANR-10-IDEX-0002-02. A.P.L.M. and L.R.M. are supported by an Australian Postgraduate Award, T.J.E. is supported by a University of Queensland Research Scholarship, and A.P. is supported by a QBI PhD scholarship. S.H. and A.Q. are respectively supported by a master's and a doctoral grant from the Fondation pour la Recherche Medicale (FRM). M.B. is supported by an NHMRC Senior Research Fellowship and an NHMRC Program Grant (GNT1054618). E.H.S. is supported by a grant from the NIH (2R01NS058721), and R.J.L. is supported by a Melbourne Children's Clinician Scientist Fellowship. L.J.R. is supported by an NMHRC Principal Research Fellowship, and P.J.L. is supported by an NHMRC Career Development Fellowship (GNT1032364). C.D. and C.N. are supported as members of the Bio-Psy Labex. This work was supported in part by the Victorian Government's Operational Infrastructure Support Program and Australian Government NHMRC IRIISS.