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

Marie-Laure Vuillaume; Mederic Jeanne; Li Xue; Sophie Blesson; Anne-Sophie Denomme-Pichon; Servane Alirol; Celine Brulard; Estelle Colin; Bertrand Isidor; Brigitte Gilbert-Dussardier; Sylvie Odent; Philippe Parent; Audrey Donnart; Richard Redon; Stephane Bezieau; Philippe Rondard; Frederic Laumonnier; Annick Toutain

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 Imagerie et cerveau

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 Génétique Médicale [CHU Poitiers]

8 CHU Pontchaillou [Rennes]

9 IGDR - Institut de Génétique et Développement de Rennes

10 CHU - BREST - Hôpital de la Cavale Blanche - CHRU Brest

11 ITX - unité de recherche de l'institut du thorax UMR1087 UMR6291

12 CHU Nantes - Centre hospitalier universitaire de Nantes

13 CRCINA - Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers

Abstract : 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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Genetics

Complete list of metadatas

Cited literature [9 references] Display Hide Download

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01730199
Contributor : Xavier Chard-Hutchinson <>
Submitted on : Thursday, December 13, 2018 - 10:03:13 AM
Last modification on : Tuesday, May 28, 2019 - 2:12:02 PM
Long-term archiving on : Thursday, March 14, 2019 - 1:36:47 PM

Vuillaume et al_A novel mutati...

Files produced by the author(s)

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

File

Identifiers

Collections

Citation

Export

Metrics

581

173

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

File

Identifiers

Collections

Citation

Export

Share

Metrics

581

173