<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>The high frequency (3.0-5.0%) of congenital anomalies (CA) and intellectual disabilities (IDs), make them a serious problem, responsible for a high percentage (33.0%) of neonatal mortality. The genetic cause remains unclear in 40.0% of cases. Recently, molecular karyotyping has become the most powerful method for detection of pathogenic imbalances in patients with multiple CAs and IDs. This method is with high resolution and gives us the opportunity to investigate and identify candidate genes that could explain the genotype-phenotype correlations. This article describes the results from analysis of 81 patients with congenital malformations (CMs), developmental delay (DD) and ID, in which we utilized the CytoChip ISCA oligo microarray, 4 × 44 k, covering the whole genome with a resolution of 70 kb. In the selected group of patients with CAs, 280 copy number variations (CNVs) have been proven, 41 were pathogenic, 118 benign and 121 of unknown clinical significance (average number of variations 3.5). In six patients with established pathogenic variations, our data revealed eight pathogenic aberrations associated with the corresponding phenotype. The interpretation of the other CNVs was made on the basis of their frequency in the investigated group, the size of the variation, content of genes in the region and the type of the CNVs (deletion or duplication).</p>
</abstract>

The high frequency (3.0-5.0%) of congenital anomalies (CA) and intellectual disabilities (IDs), make them a serious problem, responsible for a high percentage (33.0%) of neonatal mortality. The genetic cause remains unclear in 40.0% of cases. Recently, molecular karyotyping has become the most powerful method for detection of pathogenic imbalances in patients with multiple CAs and IDs. This method is with high resolution and gives us the opportunity to investigate and identify candidate genes that could explain the genotype-phenotype correlations. This article describes the results from analysis of 81 patients with congenital malformations (CMs), developmental delay (DD) and ID, in which we utilized the CytoChip ISCA oligo microarray, 4 × 44 k, covering the whole genome with a resolution of 70 kb. In the selected group of patients with CAs, 280 copy number variations (CNVs) have been proven, 41 were pathogenic, 118 benign and 121 of unknown clinical significance (average number of variations 3.5). In six patients with established pathogenic variations, our data revealed eight pathogenic aberrations associated with the corresponding phenotype. The interpretation of the other CNVs was made on the basis of their frequency in the investigated group, the size of the variation, content of genes in the region and the type of the CNVs (deletion or duplication).

Benign, pathogenic and copy number variations of unknown clinical significance in patients with congenital malformations and developmental delay

Balkan Journal of Medical Genetics

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The high frequency (3.0-5.0%) of congenital anomalies (CA) and intellectual disabilities (IDs), make them a serious problem, responsible for a high percentage...

Benign, pathogenic and copy number variations of unknown clinical significance in patients with congenital malformations and developmental delay

Article Category: Original Article

Published Online: Jun 30, 2017

Page range: 5 - 12

DOI: https://doi.org/10.1515/bjmg-2017-0010

Keywords
Microarray comparative genomic hybridization (aCGH), Congenital anomalies (CAs), Copy number variations (CNVs)

© 2017 Mihaylova M, Staneva R, Toncheva D, Pancheva M, Hadjidekova S

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Benign, pathogenic and copy number variations of unknown clinical significance in patients with congenital malformations and developmental delay

Article Category: Original Article

Published Online: Jun 30, 2017

Page range: 5 - 12

DOI: https://doi.org/10.1515/bjmg-2017-0010

KeywordsMicroarray comparative genomic hybridization (aCGH), Congenital anomalies (CAs), Copy number variations (CNVs)

© 2017 Mihaylova M, Staneva R, Toncheva D, Pancheva M, Hadjidekova S

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
Microarray comparative genomic hybridization (aCGH), Congenital anomalies (CAs), Copy number variations (CNVs)