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

AI Article Synopsis

  • - Inspired by previous research on the CYP19A1 gene and its link to speech and language disorders, studies were conducted to investigate its role as a potential contributor to dyslexia and related conditions.
  • - The CYP19A1 gene encodes the aromatase enzyme, which plays critical roles in brain development, estrogen synthesis, and even vocalization in certain animals, affecting various cognitive functions related to language and reading.
  • - Findings indicate that variations in CYP19A1 are associated with dyslexia and other language skills, with potential regulatory impacts on its expression that correlate with known dyslexia susceptibility genes and developmental brain changes observed in both mice and dyslexic individuals.

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375077PMC
http://dx.doi.org/10.1007/s10519-012-9532-3DOI Listing

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