Chromosome 15q11-13 abnormalities and other medical conditions in individuals with autism spectrum disorders

Abstract

The overall rate of possibly causal medical and cytogenetic conditions in children with autism spectrum disorders was low and no different from the rate of disorder in children with other developmental/neuropsychiatric disorders that attended the same clinics. Further research is required to determine whether paternal duplication of 15q11-13 gives rise to adverse developmental outcomes.

Advances in Autism Research – The Genomic Basis of ASD

“…It has been estimated that up to ~5% of cases of ASD can be attributed to maternal duplication of the genomic region reciprocal to the PWS-AS critical region on chromosome 15q11-13, making it one of the most common chromosomal abnormalities observed in patients with ASD [10,62]. Due to the presence of imprinting at this locus (discussed above), parent-of-origin effects are seen, and, for interstitial duplications, maternal origin confers an increased risk for clinical phenotypes.…”

“…In fact, it is now becoming increasingly evident that CNVs account for a larger proportion of new autism diagnoses than single-gene disorders. Recurrent CNVs at specific genomic loci have been associated with autism, including 15q11-q13, 16p11.2, 17p11.2, 22q13.3, 7q11.23, and 2q37, among others [1,[10][11][12][13][14][15][16]. While several of these loci are associated with known Centers for Mendelian Genomics, numerous CNVs have also been observed in idiopathic autism, underscoring the importance of these structural variations in the future of all types of autism research [17].…”

Characterization of the of the Pathological and Biochemical Markers That Correlate to the Clinical Features of Autism. Subproject 2. Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

“…A few subjects have been diagnosed with duplications of paternal origin; however, they were described as clinically unaffected (Bolton et al, 2001;Cook EH et al, 1997;Mohandas et al, 1999;Schroer et al, 1998) or affected but without ASD (Mao et al, 2000;Mohandas et al, 1999). In only one subject was paternal origin dup (15) associated with ASD (Bolton et al, 2004). Because only maternally inherited aberrations of chromosome 15q11q13 have been reported to be associated with a severe clinical phenotype, one may assume that the copy number of maternal genes within this genomic region contributes to alterations of brain development and the autistic phenotype.…”

An association analysis of candidate genes on chromosome 15 q11–13 and autism spectrum disorder

“…1 Evidence for this comes from reports that autistic symptoms are common in patients with chromosomal abnormalities of this region, especially if there is duplications of the maternally derived chromosome 15, as outlined in Bolton et al 2 There have also been a number of suggestive linkage findings. [3][4][5][6][7] Our group had marginally suggestive results from an association analysis of ASD with five microsatellite markers spread across the PWACR.…”

“…23, 24 The ASD sample tested in this study is described in detail elsewhere. 2 Briefly, the sample consists of 123 trios and 25 parent -child pairs -a total of 148 families. The probands were assessed using the ADI-R and the ADOS-G. 25,26 All subjects fulfilled criteria for a pervasive developmental disorder (PDD); 82 met the criteria for autism and the remainder had atypical autism, Asperger's syndrome or other PDD (ICD-10).…”