ARX and other single genes in X-linked mental retardation: revisiting a population-based study

Abstract

It has been calculated that monogenic genes for Xlinked mental retardation (XLMR) account for <10% of male MR [1]. XLMR can be classified as syndromic, referring to conditions with distinct neurological, physical or biochemical abnormalities, or nonsyndromic (unspecified or nonspecific). More than 20 genes are known to be associated with syndromic XLMR [2] and 13 genes have so far been identified with nonsyndromic XLMR [3]. The most common XLMR condition, fragile X syndrome (FRAXA) due to mutation in the FMR1 gene, occurs in approximately 1 in 6000 males in various populations, or in 2–2.5% in cohorts of MR males [4]. Although the search for genes has been very active in recent years, mutations in a “major” causative gene underlying a larger proportion of unexplained XLMR remain to be identified. Recently, the identification of mutations in the Aristaless related homeobox gene (ARX) in syndromic as well as non syndromic conditions [5,6] created optimism that ARX could be a major gene in XLMR, particularly since the phenotypic range