Mutations in the gene coding for methyl‐CpG‐binding protein 2 (MECP2) cause Rett syndrome (RTT) and have also been reported in a number of X‐linked mental retardation syndromes. Furthermore, putative mutations recently have been described in a few autistic patients and a boy with language disorder and schizophrenia. In this study, DNA samples from individuals with schizophrenia and other psychiatric diseases were scanned in order to explore whether the phenotypic spectrum of mutations in the MECP2 gene can extend beyond the traditional diagnoses of RTT in females and severe neonatal encephalopathy in males. The coding regions, adjacent splicing junctions, and highly conserved segments of the 3′‐untranslated region (3′‐UTR) were examined in 214 patients, including 106 with schizophrenia, 24 with autism, and 84 patients with other psychiatric diseases by detection of virtually all mutations‐single strand conformation polymorphism (SSCP) (DOVAM‐S). To our knowledge, this is the first analysis of variants in conserved regions of the 3′‐UTR of this gene. A total of 5.2 kb per haploid gene was analyzed (1.5 Mb for 214 patients). A higher frequency of missense and 3′‐UTR variants was found in autism. One missense and two 3′‐UTR variants were found in 24 patients with autism versus one patient with a missense change in 144 ethnically similar individuals without autism (P = 0.009). These mutations suggest that a possible association between MECP2 mutations and autism may warrant further study. © 2004 Wiley‐Liss, Inc.