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

Details

Serval ID
serval:BIB_9714E66E38AE
Type
Article: article from journal or magazin.
Collection
Publications
Title
The aromatase gene CYP19A1: several genetic and functional lines of evidence supporting a role in reading, speech and language.
Journal
Behavior Genetics
Author(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
Publication state
Published
Issued date
2012
Volume
42
Number
4
Pages
509-527
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
31/10/2013 16:18
Last modification date
20/08/2019 14:59
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