Partial tetrasomy of the proximal long arm of chromosome 15 in two patients: the significance of the gene dosage in terms of phenotype

Molecular Cytogenetics

Bela Melegh¹  Katalin Komlosi¹  Balazs Duga¹  Kinga Hadzsiev¹  Marta Czako¹  Andras Szabo¹ 

[1] Szentagothai Research Centre, Ifjusag 20, Pecs, H-7624, Hungary

关键词: Supernumerary chromosome;    15q duplication syndrome;    Dysmorphism;    Epilepsy;    Array CGH;   

Others  :  1221600
DOI  :  10.1186/s13039-015-0137-4

 received in 2015-02-27, accepted in 2015-04-21,  发布年份 2015

【 摘 要 】

Background

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.

Results

Here 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.

Conclusions

Dosage 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.

【 授权许可】

   
2015 Szabo et al.

【 图 表 】

Figure 1.

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Figure 3.

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