| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xq28 | {Autism susceptibility, X-linked 3} | 300496 | X-linked | 3 | MECP2 | 300005 |
A number sign (#) is used with this entry because X-linked autism-3 (AUTSX3) is associated with mutation in the MECP2 gene (300005) on Xq28.
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006).
For a discussion of genetic heterogeneity of autism, see 209850.
Lam et al. (2000) and Carney et al. (2001) identified mutations in the MECP2 gene in sporadic cases of autism, whereas no mutations in the MECP2 gene were found in a sample of 59 autistic individuals by Vourc'h et al. (2001). In 2 of 69 females with autism, Carney et al. (2003) identified 2 different de novo mutations in the MECP2 gene (300005.0011; 300005.0012).
In 2 brothers with autism, Yu et al. (2013) identified a nonsense mutation in the MECP2 gene (E483X; 300005.0039) that had been inherited from their unaffected mother. The mutation was a late truncation that was predicted to remove only the last 4 amino acids of the full-length protein, which accounted for the brothers' survival and their mild phenotypic manifestations.
Bailey, A., Phillips, W., Rutter, M. Autism: towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives. J. Child Psychol. Psychiat. 37: 89-126, 1996. [PubMed: 8655659] [Full Text: https://doi.org/10.1111/j.1469-7610.1996.tb01381.x]
Carney, R. J., Vance, J. M., Dancel, R. D., Wolpert, C. M., DeLong, G. R., McLain, C., von Wendt, L., Gilbert, J. R., Donelly, S. L., Ravan, S. A., Abel, H. L., Abramson, R. K., Wright, H. H., Zoghbi, H. Y., Cuccaro, M. L., Pericac-Vance, M. A. Screening for MECP2 mutations in females with autistic disorder. Europ. J. Hum. Genet. 9: P1329 only, 2001.
Carney, R. M., Wolpert, C. M., Ravan, S. A., Shahbazian, M., Ashley-Koch, A., Cuccaro, M. L., Vance, J. M., Pericak-Vance, M. A. Identification of MeCP2 mutations in a series of females with autistic disorder. Pediat. Neurol. 28: 205-211, 2003. [PubMed: 12770674] [Full Text: https://doi.org/10.1016/s0887-8994(02)00624-0]
Jones, J. R., Skinner, C., Friez, M. J., Schwartz, C. E., Stevenson, R. E. Hypothesis: dysregulation of methylation of brain-expressed genes on the X chromosome and autism spectrum disorders. Am. J. Med. Genet. 146A: 2213-2220, 2008. [PubMed: 18698615] [Full Text: https://doi.org/10.1002/ajmg.a.32396]
Lam, C. W., Yeung, W. L., Ko, C. H., Poon, P. M., Tong, S. F., Chan, K. Y., Lo, I. F., Chan, L. Y., Hui, J., Wong, V., Pang, C. P., Lo, Y. M., Fok, T. F. Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. J. Med. Genet. 37: E41, 2000. [PubMed: 11106359] [Full Text: https://doi.org/10.1136/jmg.37.12.e41]
Risch, N., Spiker, D., Lotspeich, L., Nouri, N., Hinds, D., Hallmayer, J., Kalaydjieva, L., McCague, P., Dimiceli, S., Pitts, T., Nguyen, L., Yang, J., and 19 others. A genomic screen of autism: evidence for a multilocus etiology. Am. J. Hum. Genet. 65: 493-507, 1999. [PubMed: 10417292] [Full Text: https://doi.org/10.1086/302497]
Schellenberg, G. D., Dawson, G., Sung, Y. J., Estes, A., Munson, J., Rosenthal, E., Rothstein, J., Flodman, P., Smith, M., Coon, H., Leong, L., Yu, C.-E., Stodgell, C., Rodier, P. M., Spence, M. A., Minshew, N., McMahon, W. M., Wijsman, E. M. Evidence for multiple loci from a genome scan of autism kindreds. Molec. Psychiat. 11: 1049-1060, 2006. [PubMed: 16880825] [Full Text: https://doi.org/10.1038/sj.mp.4001874]
Vourc'h, P., Bienvenu, T., Beldjord, C., Chelly, J., Barthelemy, C., Muh, J. P., Andres, C. No mutations in the coding region of the Rett syndrome gene MECP2 in 59 autistic patients. Europ. J. Hum. Genet. 9: 556-558, 2001. [PubMed: 11464249] [Full Text: https://doi.org/10.1038/sj.ejhg.5200660]
Yu, T. W., Chahrour, M. H., Coulter, M. E., Jiralerspong, S., Okamura-Ikeda, K., Ataman, B., Schmitz-Abe, K., Harmin, D. A., Adli, M., Malik, A. N., D'Gama, A. M., Lim, E. T., and 37 others. Using whole-exome sequencing to identify inherited causes of autism. Neuron 77: 259-273, 2013. [PubMed: 23352163] [Full Text: https://doi.org/10.1016/j.neuron.2012.11.002]