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A novel mutation in the transmembrane 6 domain of GABBR2 leads to a Rett‐like phenotype
Author(s) -
Vuillaume MarieLaure,
Jeanne Médéric,
Xue Li,
Blesson Sophie,
DenomméPichon AnneSophie,
Alirol Servane,
Brulard Céline,
Colin Estelle,
Isidor Bertrand,
GilbertDussardier Brigitte,
Odent Sylvie,
Parent Philippe,
Donnart Audrey,
Redon Richard,
Bézieau Stéphane,
Rondard Philippe,
Laumonnier Frédéric,
Toutain Annick
Publication year - 2018
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25155
Subject(s) - phenotype , rett syndrome , mutation , genetics , clinical phenotype , biology , medicine , neuroscience , gene
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.