2. Academic Validation
  3. Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome

Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome

  • Eur J Hum Genet. 2013 Jun;21(6):637-42. doi: 10.1038/ejhg.2012.226.
Olga S Koutsopoulos 1,  Christine Kretz,  Claudia M Weller,  Aurelien Roux,  Halina Mojzisova,  Johann Böhm,  Catherine Koch,  Anne Toussaint,  Emilie Heckel,  Daphne Stemkens,  Simone A J Ter Horst,  Christelle Thibault,  Muriel Koch,  Syed Q Mehdi,  Emilia K Bijlsma,  Jean-Louis Mandel,  Julien Vermot,  Jocelyn Laporte
Affiliations

Affiliation

  • 1 Department of Translational Medicine and Neurogenetics, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Illkirch, France.
PMID: 23092955 DOI: 10.1038/ejhg.2012.226
Abstract

Heterozygous mutations in Dynamin 2 (DNM2) have been linked to dominant Charcot-Marie-Tooth neuropathy and centronuclear myopathy. We report the first homozygous mutation in the DNM2 protein p.Phe379Val, in three consanguineous patients with a lethal congenital syndrome associating akinesia, joint contractures, hypotonia, skeletal abnormalities, and brain and retinal hemorrhages. In vitro membrane tubulation, trafficking and GTPase assays are consistent with an impact of the DNM2p.Phe379Val mutation on endocytosis. Although DNM2 has been previously implicated in axonal and muscle maintenance, the clinical manifestation in our patients taken together with our expression analysis profile during mouse embryogenesis and knockdown approaches in zebrafish resulting in defects in muscle organization and angiogenesis support a pleiotropic role for DNM2 during fetal development in vertebrates and humans.

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