Genetics of autosomal recessive non-syndromic mental retardation: recent advances.

The identification of the genes mutated in autosomal recessive non-syndromic mental retardation (ARNSMR) has been very active recently. This report presents an overview of the current knowledge on clinical data in ARNSMR and progress in research. To date, 12 ARNSMR loci have been mapped, and three genes identified. Mutations in known ARNSMR genes have been detected so far in only a small number of families; their contribution to mental retardation in the general population might be limited. The ARNSMR-causing genes belong to different protein families, including serine proteases, Adenosine 5'-triphosphate-dependent Lon proteases and calcium-regulated transcriptional repressors. All of the mutations in the ARNSMR-causing genes are protein truncating, indicating a putative severe loss-of-function effect. The future objective will be the development of diagnostic kits for molecular diagnosis in mentally retarded individuals in order to offer at-risk families pre-natal diagnosis to detect affected offspring.