Abstract
Among human supernumerary marker chromosomes, the occurrence of isodicentric form of 15 origin is relatively well known due to its high frequency, both in terms of gene content and associated clinical symptoms. The associated epilepsy and autism are typically more severe than in cases with interstitial 15q duplication, despite copy number gain of approximately the same genomic region. Other mechanisms besides segmental aneuploidy and epigenetic changes may also cause this difference. Among the factors influencing the expression of members of the GABAA gene cluster, the imprinting effect and copy number differences has been debated. Limited numbers of studies investigate factors influencing the interaction of GABAA cluster homologues. Five isodicentric (15) patients are reported with heterogeneous symptoms, and structural differences of their isodicentric chromosomes based on array comparative genomic hybridization results. Relations between the structure and the heterogeneous clinical picture are discussed, raising the possibility that the structure of the isodicentric (15), which has an asymmetric breakpoint and consequently a lower copy number segment, would be the basis of the imbalance of the GABAA homologues. Studies of trans interaction and regulation of GABAA cluster homologues are needed to resolve this issue, considering copy number differences within the isodicentric chromosome 15.
Highlights
A wide variety of constitutional supernumerary marker chromosomes (SMCs) have been described in the human genome, with birth prevalence of 2–7 per 10,000 [1]
We report five idic(15) cases diagnosed at where the diagnosis was confirmed and completed by array comparative genomic genomic hybridization hybridization (CGH) in each case
Due to the presence of the SMC, metaphase fluorescence in situ hybridization (FISH) analysis of the UBE3A locus (Prader–Willi/Angelman Critical Region) clinical symptoms and the presence of the SMC, metaphase FISH analysis of the UBE3A locus was performed in each case that showed the presence of both, the D15Z1 and UBE3A regions on the SMCs (Prader–Willi/Angelman Critical Region) was performed in each case that showed the presence of, thereby confirming that the extra chromosome is of 15 origin both, the D15Z1 and UBE3A regions on the SMCs
Summary
A wide variety of constitutional supernumerary marker chromosomes (SMCs) have been described in the human genome, with birth prevalence of 2–7 per 10,000 [1]. About half of the SMCs in humans are of 15 origins due to instability of 15q11.2–q13 genomic region. In the background of frequent rearrangements, there are five clusters of low copy repeats which are the basis of recurrent breakpoints known as BP1–BP5 being detected in the derivative chromosomes arising through different recombination events (non-allelic homologous recombination). U-type exchange is one of the crossovers which can result in a supernumerary isodicentric chromosome. 15 (idic(15)) showing remarkable structural heterogeneity [3]. The most often described breakpoints involved in large idic(15) are BP4 and BP5 with two extra copies of genomic regions between BP2-BP3
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