TY - JOUR
T1 - The aromatase gene CYP19A1: several genetic and functional lines of evidence supporting a role in reading, speech and language
AU - Anthoni, Heidi
AU - Sucheston, Lara E
AU - Lewis, Barbara A
AU - Tapia-Paez, Isabel
AU - Fan, Xiaotang
AU - Zucchelli, Marco
AU - Taipale, Mikko
AU - Stein, Catherine M
AU - Hokkanen, Marie-Estelle
AU - Castren, Eero
AU - Pennington, Bruce F
AU - Smith, Shelley D
AU - Olson, Richard K
AU - Tomblin, J Bruce
AU - Schulte-Korne, Gerd
AU - Nothen, Markus
AU - Schumacher, Johannes
AU - Muller-Myhsok, Bertram
AU - Hoffmann, Per
AU - Gilger, Jeffrey W
AU - Hynd, George W
AU - Nopola-Hemmi, Jaana
AU - Leppanen, Paavo H T
AU - Lyytinen, Heikki
AU - Schoumans, Jacqueline
AU - Nordenskjold, Magnus
AU - Spencer, Jason
AU - Stanic, Davor
AU - Boon, Wah Chin
AU - Simpson, Evan R
AU - Makela, Sari
AU - Gustafsson, Jan-Aake
AU - Peyrard-Janvid, Myriam
AU - Iyengar, Sudha
AU - Kere, Juha
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375077/pdf/10519_2012_Article_9532.pdf
U2 - 10.1007/s10519-012-9532-3
DO - 10.1007/s10519-012-9532-3
M3 - Article
VL - 42
SP - 509
EP - 527
JO - Behavior Genetics
JF - Behavior Genetics
SN - 0001-8244
IS - 4
ER -