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The Aromatase Gene CYP19A1: Several Genetic and Functional Lines of Evidence Supporting a Role in Reading, Speech and Language

Content Provider	Springer Nature Link
Author	Anthoni, Heidi Sucheston, Lara E. Lewis, Barbara A. Tapia Páez, Isabel Fan, Xiaotang Zucchelli, Marco Taipale, Mikko Stein, Catherine M. Hokkanen, Marie Estelle Castrén, Eero Pennington, Bruce F. Smith, Shelley D. Olson, Richard K. Tomblin, J. Bruce Schulte Körne, Gerd Nöthen, Markus Schumacher, Johannes Müller Myhsok, Bertram Hoffmann, Per Gilger, Jeffrey W. Hynd, George W. pola Hemmi, Jaana Leppanen, Paavo H. T. Lyytinen, Heikki Schoumans, Jacqueline rdenskjöld, Magnus Spencer, Jason Stanic, Davor Boon, Wah Chin Simpson, Evan Mäkelä, Sari Gustafsson, Jan Åke Peyrard Janvid, Myriam Iyengar, Sudha Kere, Juha
Copyright Year	2012
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.
Starting Page	509
Ending Page	527
Page Count	19
File Format	PDF
ISSN	00018244
Journal	Behavior Genetics
Volume Number	42
Issue Number	4
e-ISSN	15733297
Language	English
Publisher	Springer US
Publisher Date	2012-03-17
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Dyslexia SSD SLI Estrogen synthesis Translocation breakpoint Quantitative trait analysis Categorical trait association Public Health/Gesundheitswesen Health Psychology Clinical Psychology
Content Type	Text
Resource Type	Article
Subject	Genetics Ecology, Evolution, Behavior and Systematics Genetics (clinical)

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The Aromatase Gene CYP19A1: Several Genetic and Functional Lines of Evidence Supporting a Role in Reading, Speech and Language