CAMH also discovered the previously unidentified gene that causes this disorder, CC2D2A. This scientific advance will help understand the developmental and biological processes involved in brain development, and may help identify ways to diagnose and treat intellectual disabilities.

Under the direction of Dr. John Vincent, scientist at CAMH, the team identified a mutation in CC2D2A that causes the production of a shortened protein missing the C2, or calcium-binding, domain. This protein mutation results in faulty cell function, which leads to MR with RP.

Most genes for intellectual disabilities that have been found so far are on the X chromosome. As Dr. Vincent explains, this mutation was found on the autosome (The 22 pairs of non-sex chromosomes, that make up the 46 chromosomes in the human body). Autosomal-recessive inheritance (where both mother and father carry a gene mutation on one chromosome, but both maternal and paternal copies must be passed on to the offspring to cause the disorder) is believed to be relatively common in intellectual disability, though only four genes causing this type of disability have been identified to date.

What ™s really exciting is that the new gene, CC2D2A, encodes a protein with domains similar to those found in one of the previous four autosomal recessive MR genes. This link could suggest a common function that is essential for normal brain development, says Dr. Vincent.

Dr. Vincent and his team will continue exploring these initial findings, to help identify more people with mutations affecting the CC2D2A gene. This additional research will provide scientists more clues to understand, diagnose and treat intellectual disabilities.

Intellectual disabilities, also known as developmental delay or mental retardation, are a group of disorders defined by deficits in cognitive and adaptive development. Impacting between one and three percent of the population, a higher proportion of men are affected by this type of disability.

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HNF1A is produced in the liver and pancreas, where it regulates the activity of other genes, he explained. An earlier study also showed that the promoter region of the human CRP gene contains an HNF1A-binding site.

"Our finding that HNF1A polymorphism significantly impacts upon CRP levels would appear to have a strong functional basis," Ridker said. His team also uncovered links between CRP levels and the inflammatory cytokine known as interleukin-6 as well as a site in or near the gene encoding leptin, a fat-produced hormone that regulates appetite and metabolism. Both studies also found links between blood CRP levels and the CRP gene itself in addition to the apolipoprotein E (APOE) gene, consistent with earlier reports.

"The protein products of six of the seven loci [we've uncovered] are directly involved in metabolic syndrome, insulin resistance, [insulin-producing] beta-cell function, weight homeostasis, and/or premature atherothrombosis," Ridker's team concluded. "Thus, common variation in several genes involved in metabolic and inflammatory regulation have significant effects on CRP levels, consistent with CRP's identification as a useful biomarker of risk for incident vascular disease and diabetes."

"Together, these observations suggest the possibility that CRP and metabolic phenotypes may, at least in part, be under coordinate genetic control," Reiner and his colleagues said. "Given the association between plasma CRP concentration and various metabolic and cardiovascular diseases, larger studies assessing the potential association of HNF1A genotype with more complex, clinical disease-related endpoints may shed additional light on the role of genetic regulation of CRP in the occurrence of disorders such as myocardial infarction, stroke, diabetes, and metabolic syndrome."

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