Mutations in mental retardation

The genetic and molecular basis of mental retardation, which may affect up to 3% of the human population, is unclear. In the June 28 Science, Vervoort et al. report that mutations in the AGTR2 gene, encoding the angiotensin II receptor may affect cognitive function in people with X-linked mental retardation (XLMR; Science 2002, 296:2401-2403). Linkage analysis of XLMR families suggested that the Xq23-25 region might contain more than one gene related to the disease. Vervoort et al. studied translocation breakpoints in a female patient with mild retardation (with an IQ of 44); they examined expression of several candidate genes in the breakpoint region and found that the AGTR2 gene was silenced. They then screened affected males in several XLMR families and found one with a mutation in the AGTR2 gene that results in a truncated protein. Additional retardation patients with were also found AGTR2 mutations in the extracellular and intracellular domains of the receptor. The functional role of the angiotensin-renin system in brain function thus merits further investigation.