Duplications of chromosome 15 have been reported in individuals with atypical autism, varying degrees of mental retardation, and epilepsy. The authors report the molecular analysis, neurophysiologic, and clinical evaluation of a 12-year-old boy with atypical autism and epilepsy due to a maternally derived 15q11-q13 duplication. Their findings suggest that this chromosomal region harbors genes for autism and possibly for partial epilepsy that may act in a dose-dependent manner.

A number of observations point to chromosome 15 as a good candidate to harbor genes involved in epilepsy. This hypothesis is supported by at least two lines of evidence: one is the finding that haploinsufficiency of the 15q11-q13 region, of maternal origin, is responsible for Angelman syndrome, one of the cardinal manifestations of which is epilepsy; the second is the observation that extra copies of this same genomic region, in the form of inv-dup(15) or intrachromosomal duplications, again of maternal origin, are usually associated with a severe neurological phenotype characterized by developmental delay and untreatable seizures. Therefore, both reduced and increased dosage of genes from the 15q11-q13 region, possibly subjected to maternal imprinting, appear to be causally involved in severe forms of epilepsy. We tested the hypothesis that submicroscopic rearrangements of this genomic region might be responsible for nonsyndromic epilepsy in both familial and sporadic forms. To this purpose, we genotyped 118 epileptic patients and their parents with closely spaced microsatellite markers mapped within the 15q11-q13 region. We report on the results of these studies and review the relevant literature.

Imprinted genes are expressed from only one of the two parental alleles: they are located in a few, specific chromosomal regions. The parental‐specific expression is obtained through epigenetic modifications (DNA methylation, histone tail modifications) which alter the conformation of chromatin fibre and therefore regulate the expression of the underlying genes. Deletions, duplications, mutations or imprinting defects of the only active allele, as well as uniparental disomy or loss of imprinting of the inactive allele lead to an unbalance (loss of function or gain of function) in the dosage of the gene product and do have phenotypic consequences. Two such examples in human pathology are represented by the Prader–Willi and Angelman syndromes, two phenotypically different conditions, whose phenotypes result from loss of paternal or maternal contribution of the 15q11–q13 genomic region, respectively. Key Concepts: Prader–Willi and Angelman syndromes are caused by loss of function of different genes located in a genomic region under the control of a single, bipartite imprinting centre. These two condition represent the prototype of genomic imprinting disorders in humans. Genomic imprinting regulates allelic expression according to the parental origin. Imprinted genes are commonly expressed in half dosage. Imprinted genes can be inactivated by different mechanisms: uniparental disomy, microdeletion, gene mutation, primary or secondary epigenetic mutation of the imprinting centre.