Journal article

Dymeclin deficiency causes postnatal microcephaly, hypomyelination and reticulum-to-Golgi trafficking defects in mice and humans

Nina Dupuis, Assia Fafouri, Aurelien Bayot, Manoj Kumar, Tifenn Lecharpentier, Gareth Ball, David Edwards, Veronique Bernard, Pascal Dournaud, Severine Drunat, Marie Vermelle-Andrzejewski, Catheline Vilain, Marc Abramowicz, Julie Desir, Jacky Bonaventure, Nelly Gareil, Gaelle Boncompain, Zsolt Csaba, Franck Perez, Sandrine Passemard Show all

Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2015

Abstract

Dymeclin is a Golgi-associated protein whose deficiency causes Dyggve-Melchior-Clausen syndrome (DMC, MIM #223800), a rare recessively inherited spondyloepimetaphyseal dysplasia consistently associated with postnatal microcephaly and intellectual disability. While the skeletal phenotype of DMC patients has been extensively described, very little is known about their cerebral anomalies, which result in brain growth defects and cognitive dysfunction. We used Dymeclin-deficient mice to determine the cause of microcephaly and to identify defective mechanisms at the cellular level. Brain weight and volume were reduced in all mutant mice from postnatal day 5 onward. Mutant mice displayed a narrowi..

View full abstract

Grants

Awarded by French National Research Agency


Awarded by ANR


Funding Acknowledgements

This study was supported by the Institut National pour la Sante et la Recherche Medicale (Inserm), the Centre National de la Recherche Scientifique (CNRS), the Universite Paris 7, DHU PROTECT and grants from the French National Research Agency (project ANR-09-GENO-007 to V.E.G., J.B. and F.P.) and the Roger de Spoelberch Foundation. N.D. was funded by the Inserm Transfer program, M.K. was funded by the Inserm and ANR contract no. ANR-09-GENO-007.