The Aromatase Gene CYP19A1: Several Genetic and Functional Lines of Evidence Supporting a Role in Reading, Speech and Language
Year: 2012
Type: article
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.
Source: Behavior Genetics
Authors: Heidi Anthoni, Lara E. Sucheston, Barbara A. Lewis, Isabel Tapia-Páez, Xiaotang Fan, Marco Zucchelli, Mikko Taipale, Catherine M. Stein, Marie-Estelle Hokkanen, Eero Castrén, Bruce F. Pennington, Shelley D. Smith, Richard K. Olson, J. Bruce Tomblin, Gerd Schulte-Körne, Markus Nöthen, Johannes Schumacher, Bertram Müller-Myhsok, Per Hoffmann, Jeffrey W. Gilger, George W. Hynd, Jaana Nopola-Hemmi, Paavo H. T. Leppanen, Heikki Lyytinen, Jacqueline Schoumans, Magnus Nordenskjöld, Jason Spencer, Davor Stanic, Wah Chin Boon, Evan Simpson, Sari Mäkelä, Jan-Åke Gustafsson, Myriam Peyrard-Janvid, Sudha Iyengar, Juha Kere
Institutions: University of Helsinki, University at Buffalo, State University of New York, Case Western Reserve University, Karolinska Institutet, Whitehead Institute for Biomedical Research, University of Denver, University of Nebraska Medical Center, University of Colorado Boulder, University of Iowa, Ludwig-Maximilians-Universität München, University of Bonn, Max Planck Institute of Psychiatry, University of California, Merced, College of Charleston, Helsinki University Hospital, University of Jyväskylä, Karolinska University Hospital, Florey Institute of Neuroscience and Mental Health, Monash University, The University of Melbourne, University of Turku, University of Houston, Science for Life Laboratory
Language: English
Subfield: Developmental and Educational Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $3,390
Funders: European Commission, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute on Deafness and Other Communication Disorders, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Human Genetic Analysis Resource, Morphosyntactic Abilities of SLI Probands, Biometric Genetic Analysis of CardiopulmonaryDisease, Biological and Behavioral Markers of Persistent Speech Sound Disorders, Twins and Singletons with Specific Language Impairment, Differential Diagnosis in Learning Disabilities
OpenAlex ID: W2078584334