Autism, Susceptibility To, 3

Description

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.

See also chromosome 13q14 deletion syndrome (613884) in which retinoblastoma and mental retardation are features.

Cytogenetics

Ritvo et al. (1988) reported on the simultaneous occurrence of autism and retinoblastoma in a patient with a deletion that extended from 13q12 to 13q14. Steele et al. (2001) described a case of autism with a de novo deletion of 13q14-q22. The Collaborative Linkage Study of Autism (2001) analyzed the effect of incorporating language information and parental structural language phenotypes into the genome screening for autism. Their results revealed 2 distinct peaks of linkage on 13q.

In a sporadic case of autism and language deficit due to auditory processing defects, Smith et al. (2002) demonstrated an interstitial deletion in chromosome 13q. The breakpoints of the deletion were estimated to be 13q13.2 and 13q14.1. Chromosome analysis on peripheral blood from the parents revealed normal karyotypes. Smith et al. (2002) determined that the deletion occurred on the paternally derived chromosome 13. Molecular genetic studies indicated that the deletion mapped between the 2 chromosome 13 linkage peaks described by the Collaborative Linkage Study of Autism (2001) in studies of subjects with autism and language deficits. The 9-Mb region contains at least 4 genes that are expressed in brain and that play a role in brain development: neurobeachin (NBEA; 604889); MAB21L1 (601280), which maps within NBEA; DCAMKL1 (604742); and MADH9 (603295).