XLMR-affected families from the UK, United States, Australia, Europe and South Africa were included if there were two or more cases of mental retardation in males, predominant sparing of carrier females and no evidence of male-to-male transmission of mental retardation. Subjects were examined by a clinical geneticist with expertise in the field and the severity of the disease was categorized using DSM–IV or ICD-10 classifications (profound mental retardation was classified as severe). Where formal IQ testing using either the Stanford Binet or Wechsler IQ scoring was not performed, functional assessments of the degree of mental retardation were used. The individual entered into the sequencing screen was an affected male in 203 of 208 cases. Five screened individuals were obligate carrier females, all of whom were unaffected by mental retardation. Control DNAs were either from lymphoblastoid cell lines derived from adults of European ancestry from the UK without mental retardation or from filtered white cells from blood donors. XLMR-affected families and controls provided informed consent for research and the studies were reviewed and approved by ethics committees and institutional review boards of each collaborating institution.
