Abstract
BackgroundLarge amounts of low copy number repeats in the 15q11.2q13.3 chromosomal region increase the possibility of misalignments and unequal crossover during meiosis in this region, leading to deletions, duplications, triplications and supernumerary chromosomes. Most of the reported cases with epilepsy, autism and Prader-Willi/Angelman syndrome are in association with rearrangements of the proximal long arm of chromosome 15.ResultsHere we report the first two unrelated Hungarian patients with the same epileptic and dysmorphic features, who were investigated by array comparative genomic hybridization (array CGH). By G-banded karyotype followed by FISH and array CGH we could detect partial tetrasomy of the 15q11.2q13.3 chromosomal region, supporting proximal 15q duplication syndrome. Findings of the array CGH gave fully explanation of the phenotypic features of these patients, including epileptic seizures, delayed development, hyperactivity and craniofacial dysmorphic signs. Besides the described features of isodicentric (15) (idic(15)) syndrome Patient 1. suffered from bigeminic extrasystoles and had postnatal growth retardation, which had been published only in a few articles.ConclusionsDosage effect of some genes in the concerned genomic region is known, but several genes have no evidence to have dosage dependence. Our results expanded the previous literature data. We assume dosage dependence in the case of CHRNA7 and OTUD7A, which might be involved in growth regulation. On the other hand increased dosage of the KLF13 gene seems to have no direct causal relationship with heart morphology. The genomic environment of the affected genes may be responsible for the observed phenotype.Electronic supplementary materialThe online version of this article (doi:10.1186/s13039-015-0137-4) contains supplementary material, which is available to authorized users.
Highlights
Large amounts of low copy number repeats in the 15q11.2q13.3 chromosomal region increase the possibility of misalignments and unequal crossover during meiosis in this region, leading to deletions, duplications, triplications and supernumerary chromosomes
Fluorescent in situ hybridization (FISH) investigation is necessary in cases wheresatellited supernumerary chromosome is present in order to establish the chromosomal origin and the involvement of Prader-Willi/Angelman region (PWACR) in those with proven chromosome 15 material
FISH analysis followed by array Array comparative genomic hybridization (CGH) provided clinically relevant information of the investigated patients
Summary
Large amounts of low copy number repeats in the 15q11.2q13.3 chromosomal region increase the possibility of misalignments and unequal crossover during meiosis in this region, leading to deletions, duplications, triplications and supernumerary chromosomes. Most of the reported cases with epilepsy, autism and Prader-Willi/ Angelman syndrome are in association with rearrangements of the proximal long arm of chromosome 15. Karyotyping and FISH are essential parts of the clinical evaluation of patients with epilepsy and dysmorphic features. FISH investigation is necessary in cases where (bi)satellited supernumerary chromosome is present in order to establish the chromosomal origin and the involvement of Prader-Willi/Angelman region (PWACR) in those with proven chromosome 15 (chr15) material. Increasing usage of array comparative genomic hybridization (array CGH) in the examination of patients with epilepsy and dysmorphic features allows the determination of the correlation between phenotype and genotype. Small supernumerary marker chromosomes derived from the chr (sSMC(15)s) has been more frequently reported in connection with dysmorphic features and cause several phenotypes including intellectual disability, growth deficiency, triangular facies, and brachydactyly [2,3].
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