Other entities represented in this entry:
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xq13.1 | {Autism susceptibility, X-linked 1} | 300425 | X-linked | 3 | NLGN3 | 300336 |
A number sign (#) is used with this entry because susceptibility to X-linked autism-1 (AUTSX1) is conferred by variation in the NLGN3 (300336) gene on chromosome Xq13.
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.
Auranen et al. (2002) performed a 2-stage genomewide screen for autism-spectrum disorders in 38 Finnish families and found evidence for potential susceptibility loci on several chromosomes, including Xq. A maximum multipoint lod score (MLS) of 2.75 was obtained near marker DXS7132.
Shao et al. (2002) performed a 2-stage genomewide screen for autism in a total of 99 families and found evidence for susceptibility loci on chromosomes 2, 3, 7, 15, 19, and X. The locus on chromosome X yielded the highest multipoint MLS (greater than 2.0 at marker DXS6789).
In a Swedish family in which 1 brother had typical autism and another was diagnosed with Asperger syndrome, Jamain et al. (2003) identified a mutation in the NLGN3 gene (300336.0001).
Auranen, M., Vanhala, R., Varilo, T., Ayers, K., Kempas, E., Ylisaukko-oja, T., Sinsheimer, J. S., Peltonen, L., Jarvela, I. A genomewide screen for autism-spectrum disorders: evidence for a major susceptibility locus on chromosome 3q25-27. Am. J. Hum. Genet. 71: 777-790, 2002. [PubMed: 12192642] [Full Text: https://doi.org/10.1086/342720]
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]
Jamain, S., Quach, H., Betancur, C., Rastam, M., Colineaux, C., Gillberg, I. C., Soderstrom, H., Giros, B., Leboyer, M., Gillberg, C., Bourgeron, T., Paris Autism Research International Sibpair Study. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nature Genet. 34: 27-29, 2003. [PubMed: 12669065] [Full Text: https://doi.org/10.1038/ng1136]
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]
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]
Shao, Y., Wolpert, C. M., Raiford, K. L., Menold, M. M., Donnelly, S. L., Ravan, S. A., Bass, M. P., McClain, C., von Wendt, L., Vance, J. M., Abramson, R. H., Wright, H. H., Ashley-Koch, A., Gilbert, J. R., DeLong, R. G., Cuccaro, M. L., Pericak-Vance, M. A. Genomic screen and follow-up analysis for autistic disorder. Am. J. Med. Genet. 114: 99-105, 2002. [PubMed: 11840513] [Full Text: https://doi.org/10.1002/ajmg.10153]