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ZIRC
ZFIN ID: ZDB-PUB-121102-35
Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome
Koutsopoulos, O.S., Kretz, C., Weller, C.M., Roux, A., Mojzisova, H., Böhm, J., Koch, C., Toussaint, A., Heckel, E., Stemkens, D., Ter Horst, S.A., Thibault, C., Koch, M., Mehdi, S.Q., Bijlsma, E.K., Mandel, J.L., Vermot, J., and Laporte, J.
Date: 2013
Source: European journal of human genetics : EJHG 21(6): 637-42 (Journal)
Registered Authors: Vermot, Julien
Keywords: none
MeSH Terms:
  • Amino Acid Sequence
  • Amino Acid Substitution/genetics
  • Animals
  • Base Sequence
  • Congenital Abnormalities/genetics*
  • Conserved Sequence/genetics
  • DNA Mutational Analysis
  • Dynamin II/chemistry
  • Dynamin II/genetics*
  • Dynamin II/metabolism
  • Embryonic Development/genetics
  • Female
  • Gene Expression Regulation, Developmental
  • Heterozygote
  • Homozygote*
  • Humans
  • Infant, Newborn
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation, Missense/genetics*
  • Pedigree
  • Pregnancy
  • Syndrome
PubMed: 23092955 Full text @ Eur. J. Hum. Genet.
FIGURES
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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