A novel mutation in the transmembrane 6 domain of GABBR2 leads to a Rett-like phenotype

Marie-Laure Vuillaume (1, 2) , Mederic Jeanne (1, 2) , Li Xue (3) , Sophie Blesson (2) , Anne-Sophie Denomme-Pichon (4, 5) , Servane Alirol (1, 2) , Celine Brulard (1, 2) , Estelle Colin (4, 5) , Bertrand Isidor (6) , Brigitte Gilbert-Dussardier (7) , Sylvie Odent (8, 9) , Philippe Parent (10) , Audrey Donnart (11) , Richard Redon (11) , Stephane Bezieau (12, 13) , Philippe Rondard (3) , Frederic Laumonnier (1, 2) , Annick Toutain (1, 2)

1 iBraiN - Imaging, Brain & Neuropsychiatry
2 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
3 IGF - Institut de Génomique Fonctionnelle
4 BNMI - Biologie Neurovasculaire et Mitochondriale Intégrée
5 Département de Biochimie et Génétique [Angers]
6 Service de génétique médicale - Unité de génétique clinique [Nantes]
7 Service de Génétique Médicale [CHU Poitiers]
8 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
9 IGDR - Institut de Génétique et Développement de Rennes
10 CHU - BREST - Hôpital de la Cavale Blanche - CHRU Brest
11 ITX - ITX - unité de recherche de l'institut du thorax
12 CHU Nantes - Centre Hospitalier Universitaire de Nantes
13 CRCINA-ÉQUIPE 1 - Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications

We read with great interest the recent article published by Yooet al1reporting 4 additional Rett-like (RTT) patients with therecurring A567TGABBR2mutation.2More interestingly, theyshowed, with in vitro and in vivo functional studies, that theseverity of the phenotype caused byGABBR2mutations wasdirectly linked to their impact onc-aminobutyric acid (GABA)signaling activity, this latter being more reduced with the 2 mis-sense mutations, S695I and I705N, associated with epilepticencephalopathy (EE).1,3They hypothesized that the position ofvariants in different transmembrane (TM) domains ofGABBR2,TM6 for S695I and I705N, and TM3 for A567T, could deter-mine the phenotypic expression. This hypothesis was recentlyreinforced with the report of a novelGABBR2mutation also inTM6 and associated with infantile epileptic spasms.

Domaines: Génétique

Marie-Laure Vuillaume, Mederic Jeanne, Li Xue, Sophie Blesson, Anne-Sophie Denomme-Pichon, et al.. A novel mutation in the transmembrane 6 domain of GABBR2 leads to a Rett-like phenotype. Annals of Neurology, 2018, 83 (2), pp.437-439. ⟨10.1002/ana.25155⟩. ⟨hal-01730199⟩