The aromatase gene CYP19A1: several genetic and functional lines of evidence supporting a role in reading, speech and language.

Détails

ID Serval
serval:BIB_9714E66E38AE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The aromatase gene CYP19A1: several genetic and functional lines of evidence supporting a role in reading, speech and language.
Périodique
Behavior Genetics
Auteur⸱e⸱s
Anthoni H., Sucheston L.E., Lewis B.A., Tapia-Páez I., Fan X., Zucchelli M., Taipale M., Stein C.M., Hokkanen M.E., Castrén E., Pennington B.F., Smith S.D., Olson R.K., Tomblin J.B., Schulte-Körne G., Nöthen M., Schumacher J., Müller-Myhsok B., Hoffmann P., Gilger J.W., Hynd G.W., Nopola-Hemmi J., Leppanen P.H., Lyytinen H., Schoumans J., Nordenskjöld M., Spencer J., Stanic D., Boon W.C., Simpson E., Mäkelä S., Gustafsson J.Å., Peyrard-Janvid M., Iyengar S., Kere J.
ISSN
1573-3297 (Electronic)
ISSN-L
0001-8244
Statut éditorial
Publié
Date de publication
2012
Volume
42
Numéro
4
Pages
509-527
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Inspired by the localization, on 15q21.2 of the CYP19A1 gene in the linkage region of speech and language disorders, and a rare translocation in a dyslexic individual that was brought to our attention, we conducted a series of studies on the properties of CYP19A1 as a candidate gene for dyslexia and related conditions. The aromatase enzyme is a member of the cytochrome P450 super family, and it serves several key functions: it catalyzes the conversion of androgens into estrogens; during early mammalian development it controls the differentiation of specific brain areas (e.g. local estrogen synthesis in the hippocampus regulates synaptic plasticity and axonal growth); it is involved in sexual differentiation of the brain; and in songbirds and teleost fishes, it regulates vocalization. Our results suggest that variations in CYP19A1 are associated with dyslexia as a categorical trait and with quantitative measures of language and speech, such as reading, vocabulary, phonological processing and oral motor skills. Variations near the vicinity of its brain promoter region altered transcription factor binding, suggesting a regulatory role in CYP19A1 expression. CYP19A1 expression in human brain correlated with the expression of dyslexia susceptibility genes such as DYX1C1 and ROBO1. Aromatase-deficient mice displayed increased cortical neuronal density and occasional cortical heterotopias, also observed in Robo1-/- mice and human dyslexic brains, respectively. An aromatase inhibitor reduced dendritic growth in cultured rat neurons. From this broad set of evidence, we propose CYP19A1 as a candidate gene for human cognitive functions implicated in reading, speech and language.
Mots-clé
Animals, Aromatase/genetics, Aromatase/metabolism, Brain/growth & development, Brain/metabolism, Cohort Studies, Dyslexia/genetics, Dyslexia/metabolism, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Humans, Language Disorders/genetics, Language Disorders/metabolism, Male, Mice, Mice, Knockout, Nerve Tissue Proteins/genetics, Nerve Tissue Proteins/metabolism, Nuclear Proteins/genetics, Nuclear Proteins/metabolism, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Quantitative Trait Loci, RNA, Messenger/analysis, Receptors, Immunologic/genetics, Receptors, Immunologic/metabolism, Speech Disorders/genetics, Speech Disorders/metabolism, Translocation, Genetic
Pubmed
Web of science
Open Access
Oui
Création de la notice
31/10/2013 16:18
Dernière modification de la notice
20/08/2019 14:59
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