Rare ACTG1 variants in fetal microlissencephaly.
Fiche publication
Date publication
août 2015
Journal
European journal of medical genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHELLY Jamel
Tous les auteurs :
Poirier K, Martinovic J, Laquerrière A, Cavallin M, Fallet-Bianco C, Desguerre I, Valence S, Grande-Goburghun J, Francannet C, Deleuze JF, Boland A, Chelly J, Bahi-Buisson N
Lien Pubmed
Résumé
Heterozygous ACTG1 mutations are responsible for Baraitser-Winter cerebrofrontofacial syndrome which cortical malformation is characterized by pachygyria with frontal to occipital gradient of severity. We identified by whole exome sequencing in a cohort of 12 patients with prenatally diagnosed microlissencephaly, 2 foetal cases with missense mutations in the ACTG1 gene and in one case of living patient with typical Baraitser-Winter syndrome. Both foetuses and child exhibited microcephaly and facial dysmorphism consisting of microretrognatism, hypertelorism and low-set ears. Brain malformations included lissencephaly with an immature cortical plate, dysmorphic (2/3) or absent corpus callosum and vermian hypoplasia (2/3). Our results highlight the powerful diagnostic value of exome sequencing for patients with microlissencephaly, that may expand the malformation spectrum of ACTG1-related Baraitser-Winter cerebrofrontofacial syndrome and may suggest that ACTG1 could be added to the list of genes for assessing microlissencephaly.
Mots clés
Abnormalities, Multiple, diagnosis, Abortion, Eugenic, Actins, genetics, Cerebral Cortex, metabolism, Child, Craniofacial Abnormalities, diagnosis, Exome, Exons, Female, Fetus, Gene Expression, Heterozygote, High-Throughput Nucleotide Sequencing, Humans, Introns, Male, Microcephaly, diagnosis, Mutation, Missense
Référence
Eur J Med Genet. 2015 Aug;58(8):416-8