Although it is evident that a genetic factor is involved in the aetiology of MR and the genetic cause of a number of subtypes has been identified (e.g. trisomy of chromosome 21 in Down’s syndrome), the majority of cases have an unknown genetic aetiology. Since MR has a clearly X-linked inheritance pattern and is more often found in males than females, variations in the X-chromosome may increase the risk for MR. A number of X-linked genes have been identified as susceptibility genes for MR, including fragile X mental retardation 2 (FMR2; Xq28), oligophrenin 1 (OPHN1; Xq12), p21 (CDKN1A)-activated kinase 3 (PAK3; Xq22.3-23), GDP dissociation inhibitor 1 (GDI1; Xq28), Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 (ARHGEF6; Xq26), ribosomal protein S6 kinase, 90kDa, polypeptide 3 (RPS6KA3; Xp22.2-p22.1), interleukin 1 receptor accessory protein-like 1 (IL1RAPL1; Xp22.1-p21.3), tetraspanin 7 (TSPAN7; Xp11.4), methyl CpG binding protein 2 (MECP2; Xq28), acyl-CoA synthetase long-chain family member 4 (ACSL4; Xq22.3-q23) and aristaless related homeobox (ARX; Xp21) [79-89]. However, many other genes are likely linked to MR.
