known genes involved in XLMR at similar levels of significance: HUWE1 (P = 0.007), OPHN1 (P = 0.001), MED12 (0.004) and PGK1 (P = 0.002). As these genes do not show evidence of recent positive selection25, their excess variation may be due to mental retardation–causing missense variants. By contrast, zero genes known to cause diseases other than mental retardation (excluding G6PD) were highlighted. Of genes not yet implicated in a monogenic disease, only one was highlighted: SMARCA1 (P = 0.009). These results suggest that missense variants in known and possibly additional XLMR-associated genes account for the disease in a further subset of families.
