We’re totally in love with this princess”
Sophia has a retinoic acid receptor beta (RARB) gene alteration in Chromosone 3, located in exon 8. Formally seen as c.1159C>T (p.R387C) in which the Cytosine was replaced by Thymidine in nucleotide 1159 causing Arginine (R) at amino acid position 387 to be replaced by a Cysteine. RARB is a member of the thyroid-steroid hormone receptor superfamily of nuclear transcriptional regulators. The receptor localizes to cytoplasm and subnuclear compartments. It binds retinoid acid, the biologically active form of Vitamin A which mediates cellular signaling in embryonic morphogenesis, cell growth and differentiation. It is believed that this protein limits the growth of many cell types by regulating gene expression. Due to the amino acid alteration, there is a 2 to 3 fold increase in RARB transcriptional activity which suggests a gain of function and functional analysis in transfected HEK293 cells demonstrate transcriptional response to retinoid acid is significantly increased, reaching a 28 fold induction for R387C versus a 9 fold for wild type RARB. For you researchers out there, it seems to me if we can reduce transcriptional response to retinoid acid thereby suppressing the gain of function, could we then potentially see an improvement in her spasticity or other organs that have been compromised due to this gene mutation since she is still developing? Let me know what you need to run any tests and I will happily jump on that band wagon if it is at all possible!