Cytogenetic location: 17q21 Genomic coordinates (GRCh38): 17:39,800,001-52,100,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 17q21 | {Autism susceptibility 7} | 610676 | 2 |
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.
By fine mapping of markers on chromosome 17q in 56 autism-affected sib pairs from 48 independent families with only affected males, Cantor et al. (2005) found significant linkage to 17q21 (maximum lod score of 4.1 at marker D17S2180). A 1-lod score drop includes a peak from a second scan with a maximum lod score of 3.6 at D17S1299 (approximately 5 cM proximal to D17S2180). Cantor et al. (2005) noted that the ITGB3 gene on 17q21 may be a candidate autism gene because it is involved in serotonin levels, particularly in males, and is a cell adhesion molecule that may play a role in nervous system development.
Associations Pending Confirmation
Weiss et al. (2006) found a significant (p = 0.00082) association between a common allele in the ITGB3 gene (L33P; 173470.0006) and autism in a combined sample of 730 affected families. There appeared to be a sex difference. Weiss et al. (2006) presented evidence suggesting that genotypes at the ITGB3 and SLC6A4 (182138) genes may interact to affect autism susceptibility.
In a family-based association study of 281 simplex and 12 multiplex Caucasian families with autism, Napolioni et al. (2011) reported an association between autism and certain ITGB3 haplotypes. Haplotype H3 was largely overtransmitted to the affected offspring and doubled the risk of an ASD diagnosis (odds ratio (OR) of 2.0; p = 0.005), whereas haplotype H1 was undertransmitted (OR of 0.725; p = 0.018). These 2 common haplotypes differ only at rs12603582 in intron 11, located toward the 3-prime end of the ITGB3 gene. In contrast, rs2317385, located at the 5-prime end of the gene, was significantly associated with 5-HT (see 607478) blood levels. The SNP rs12603582 was strongly associated with preterm delivery in the autism patients (p = 0.008). No gene-gene interaction between ITGB3 and SLC6A4 was detected.
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