title: Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome.
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.
authors.affiliation: Department of Translational Medicine and Neurogenetics, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Illkirch, France.
authors.forename: Olga S
authors.initials: OS
authors.lastname: Koutsopoulos
authors.forename: Christine
authors.initials: C
authors.lastname: Kretz
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Weller
authors.forename: Aurelien
authors.initials: A
authors.lastname: Roux
authors.forename: Halina
authors.initials: H
authors.lastname: Mojzisova
authors.forename: Johann
authors.initials: J
authors.lastname: Böhm
authors.forename: Catherine
authors.initials: C
authors.lastname: Koch
authors.forename: Anne
authors.initials: A
authors.lastname: Toussaint
authors.forename: Emilie
authors.initials: E
authors.lastname: Heckel
authors.forename: Daphne
authors.initials: D
authors.lastname: Stemkens
authors.forename: Simone A J
authors.initials: SA
authors.lastname: Ter Horst
authors.forename: Christelle
authors.initials: C
authors.lastname: Thibault
authors.forename: Muriel
authors.initials: M
authors.lastname: Koch
authors.forename: Syed Q
authors.initials: SQ
authors.lastname: Mehdi
authors.forename: Emilia K
authors.initials: EK
authors.lastname: Bijlsma
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mandel
authors.forename: Julien
authors.initials: J
authors.lastname: Vermot
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Laporte
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D000013:Congenital Abnormalities / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D004252:DNA Mutational Analysis; D034285:Dynamin II / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D013577:Syndrome
chemical_list: D034285:Dynamin II