TY - JOUR
T1 - De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits
T2 - report of 25 new individuals and review of the literature
AU - CAUSES Study
AU - Nambot, Sophie
AU - Faivre, Laurence
AU - Mirzaa, Ghayda
AU - Thevenon, Julien
AU - Bruel, Ange Line
AU - Mosca-Boidron, Anne Laure
AU - Masurel-Paulet, Alice
AU - Goldenberg, Alice
AU - Le Meur, Nathalie
AU - Charollais, Aude
AU - Mignot, Cyril
AU - Petit, Florence
AU - Rossi, Massimiliano
AU - Metreau, Julia
AU - Layet, Valérie
AU - Amram, Daniel
AU - Boute-Bénéjean, Odile
AU - Bhoj, Elizabeth
AU - Cousin, Margot A.
AU - Kruisselbrink, Teresa M.
AU - Lanpher, Brendan C.
AU - Klee, Eric W.
AU - Fiala, Elise
AU - Grange, Dorothy K.
AU - Meschino, Wendy S.
AU - Hiatt, Susan M.
AU - Cooper, Gregory M.
AU - Olivié, Hilde
AU - Smith, Wendy E.
AU - Dumas, Meghan
AU - Lehman, Anna
AU - Adam, Shelin
AU - du Souich, Christèle
AU - Elliott, Alison M.
AU - Mwenifumbo, Jill
AU - Nelson, Tanya N.
AU - van Karnebeek, Clara
AU - Friedman, Jan M.
AU - Inglese, Cara
AU - Nizon, Mathilde
AU - Guerrini, Renzo
AU - Vetro, Annalisa
AU - Kaplan, Eitan S.
AU - Miramar, Dolores
AU - Van Gils, Julien
AU - Fergelot, Patricia
AU - Bodamer, Olaf
AU - Herkert, Johanna C.
AU - Pajusalu, Sander
AU - Õunap, Katrin
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to European Society of Human Genetics.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands.
AB - TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands.
UR - http://www.scopus.com/inward/record.url?scp=85079190399&partnerID=8YFLogxK
U2 - 10.1038/s41431-020-0571-6
DO - 10.1038/s41431-020-0571-6
M3 - Article
C2 - 32005960
AN - SCOPUS:85079190399
SN - 1018-4813
VL - 28
SP - 770
EP - 782
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 6
ER -