Diagnostic contribution of comparative genomic hybridization on microarrays in prenatal detection of genomic disorders
DOI:
https://doi.org/10.13112/pc.1056Keywords:
PRENATAL DIAGNOSIS; COMPARATIVE GENOMIC HYBRIDIZATION; ULTRASONOGRAPHY; CONGENITAL ABNORMALITIESAbstract
The aim of the study was to determine the diagnostic yield of array comparative genomic hybridization (aCGH) in detecting submicroscopic changes, as well as the occurrence of variants of uncertain significance (VUSs).
Methods included a retrospective results analysis obtained from various cytogenomic techniques on a total of 738 samples obtained by chorionic villus sampling and amniocentesis. Indications for invasive procedures included abnormal fetal ultrasound, high-risk biochemical or non-invasive screening tests, and a positive medical history for genomic disorders. Karyotyping was performed on all samples. aCGH analysis was conducted on 78 chorionic villi samples and 259 amniotic fluid samples with normal karyotype or unbalanced structural rearrangements.
Results: Among women referred for chorionic villus sampling an amniocentesis, numerical and structural chromosomal aberrations were found in 56 % and 27 % of cases, respectively. Numerical chromosomal abnormalities were detected in 32 % of fetuses, with the highest proportion of trisomy 21 and 18. Unbalanced structural rearrangements of parental origin were found in 19 fetuses, while balanced reciprocal and Robertsonian translocations were identified in 14 cases. Copy number variants (CNVs) in fetuses with a normal karyotype were found in 14 cases, of which seven were classified as pathogenic and seven as VUS. Submicroscopic pathological changes, as well as VUSs, were detected in 2.48 % of cases.
Conclusions: The use of aCGH in prenatal diagnostics has increased the diagnostic yield for CNV detection. However, a significant number of abnormalities remain undetected, particularly in fetuses with multiple malformations, suggesting the implementation of next-generation sequencing into standard practice.
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