LAUSR

Mutations in more than 100 genes have been reported to cause X-linked intellectual disability (XLID), mainly in males. By contrast, the identified X-linked genes in which de novo mutations specifically cause ID in females are still limited so far.1 Next-generation sequencing has nowadays enabled the screening for a causative mutation in XLID using targeted panel, X-exome, and whole-exome sequencing methods.2 Mutations in the X-linked cell division cycle 42 guanine nucleotide exchange factor (GEF)-9 gene (ARHGEF9) have been recently associated with a wide phenotypic spectrum, including ID, behavior disorders, autism spectrum disorder, hyperekplexia, and infantile epileptic encephalopathy.3–5 A number of patients with ARHGEF9 mutations, encompassing missense and nonsense mutations, deletions, and complex rearrangements, have been reported. However, so far, the clinical features of ARHGEF9 disease are nonspecific, with extreme phenotypic and genetic heterogeneity.