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Eur J Hum Genet. 2013 Jun;21(6):637-42. doi: 10.1038/ejhg.2012.226. Epub 2012 Oct 24.

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

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1
Department of Translational Medicine and Neurogenetics, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Illkirch, France.

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.

PMID:
23092955
PMCID:
PMC3658203
DOI:
10.1038/ejhg.2012.226
[Indexed for MEDLINE]
Free PMC Article
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