Array-comparative genomic hybridization results in clinically affected cases with apparently balanced chromosomal rearrangements

• Published in: Balkan journal of medical genetics Vol. 23; no. 2; pp. 25 - 34
• Main Authors: Satkin, NB, Karaman, B, Ergin, S, Kayserili, H, Kalelioglu, IH, Has, R, Yuksel, A, Basaran, S
• Format: Journal Article
• Language: English
• Published: Poland Sciendo 23-03-2021; De Gruyter Poland
• Subjects: Apparently balanced structural chromosomal abnormalities (ABCRs); Array-comparative genomic hybridization (aCGH); Breakpoints; Chromosomal microarray (CMA); Chromosome rearrangements; Cryptic genomic imbalances; DNA microarrays; Fetal ultrasound findings; Fetuses; Genomes; Genomic imprinting; Hybridization; Original; Phenotypes; Ultrasonic imaging; Ultrasound; Fetal ultrasound findings; Array-comparative genomic hybridization (aCGH); Apparently balanced structural chromosomal abnormalities (ABCRs); Cryptic genomic imbalances; Chromosomal microarray (CMA)
• ISSN: 1311-0160; 2199-5761; 1311-0160
• DOI: 10.2478/bjmg-2020-0026

Carriers of apparently balanced chromosomal rearrangements (ABCRs) have a 2-3-fold higher risk of carrying an abnormal phenotype, when compared to the average population. Apparently balanced chromosomal rearrangements can be imbalanced at the submicroscopic level, and changes in the gene structure, formation of a new chimeric gene, gain or loss of function of the genes and altered imprinting pattern may also affect the phenotype. Chromosomal microarray (CMA) is an efficient tool to detect submicroscopic imbalances at the breakpoints as well as in the whole genome. We aimed to determine the effectiveness of array-comparative genomic hybridization (aCGH) application in phenotypically affected cases with ABCRs at a single center from Turkey. Thirty-four affected cases (13 prenatal, 21 postnatal) carrying ABCRs were investigated with CMA. In postnatal series, ABCRs were familial in 7 and
in 14 cases. Seven
cases were imbalanced (in postnatal series 33.3% and in
cases 50.0%). Out of 13 prenatal cases, five were familial and eight were
in origin and two
cases were imbalanced (in 15.4% prenatal series and in 25.0%
cases). No cryptic imbalance was observed in familial cases. The anomaly rates with array studies ranged between 14.3-25.0% in familial and between 20.0-57.5% in
cases of postnatal series in the literature. Studies focused on prenatal ABCR cases with abnormal ultrasound findings are limited and no submicroscopic imbalance was reported in the cohorts. When
postnatal or prenatal results were combined, the percentage of abnormalities detected by CMA was 40.9%. Taking this contribution into consideration, all ABCRs should be investigated by CMA even if the fetal ultrasound findings are normal.