<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...

Patient	Chromosome	Type of Aberration	Position (bp)		Size (bp)	Cytoband
			Start	End		Start	End
79	2	deletion	50,982,143	51,314,401	332,259	2p16.3	2p16.3
79	5	deletion	175,470,501	177,136,261	1,665,761	5q35.2	5q35.3
52	10	deletion	122,804,780	135,434,149	12,629,370	10q26.12	10q26.3
46	4	deletion	178,213,959	190,896,645	12,682,687	4q34.3	4q35.2
46	12	duplication	230,451	14,111,977	13,881,527	12p13.33	12p13.1
41	17	deletion	34,450,435	36,248,889	1,798,455	17q12	17q12
35	22	deletion	21,561,492	22,905,039	1,343,548	22q11.21	22q11.22
30	15	duplication	22,765,658	29,030,488	6,264,831	15q11.2	15q13.1

Parameters	Total Number	100-500 kb	500 kb - 1 Mb	>1 Mb
Benign and CNVs of unknown clinical significance	239	179	52	8
Benign CNVs	118	90	21	7
CNVs of unknown clinical significance	121	89	31	1

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.

Figure 1

Summarized results with pathogenic findings identified after microarray comparative genomic hybridization and associated with the phenotype of the patient.

Number and size of detected benign copy number variations and copy number variations of unknown clinical significance.

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.

Figure 1

Summarized results with pathogenic findings identified after microarray comparative genomic hybridization and associated with the phenotype of the patient.

Number and size of detected benign copy number variations and copy number variations of unknown clinical significance.

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