Chromosomal microarray in postnatal diagnosis of congenital anomalies and neurodevelopmental disorders in Serbian patients.
chromosomal microarray
congenital anomalies
copy number variations
detection rate
neurodevelopmental disorders
Journal
Journal of clinical laboratory analysis
ISSN: 1098-2825
Titre abrégé: J Clin Lab Anal
Pays: United States
ID NLM: 8801384
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
revised:
04
04
2022
received:
03
03
2022
accepted:
07
04
2022
pubmed:
21
4
2022
medline:
9
6
2022
entrez:
20
4
2022
Statut:
ppublish
Résumé
Array-based genomic analysis is a gold standard for the detection of copy number variations (CNVs) as an important source of benign as well as pathogenic variations in humans. The introduction of chromosomal microarray (CMA) has led to a significant leap in diagnostics of genetically caused congenital malformations and neurodevelopmental disorders, with an average diagnostic yield of 15%. Here, we present our experience from a single laboratory perspective in four years' postnatal clinical CMA application. DNA samples of 430 patients with congenital anomalies and/or neurodevelopmental disorders were analyzed by comparative genome hybridization using oligonucleotide-based microarray platforms. Interpretation of detected CNVs was performed according to current guidelines. The detection rate (DR) of clinically significant findings (pathogenic/likely pathogenic CNVs) was calculated for the whole cohort and isolated or combined phenotypic categories. A total of 140 non-benign CNVs were detected in 113/430 patients (26.5%). In 70 patients at least one CNV was considered clinically significant thus reaching a diagnostic yield of 16.3%. The more complex the phenotype, including developmental delay/intellectual disability (DD/ID) as a prevailing feature, the higher the DR of clinically significant CNVs is obtained. Isolated congenital anomalies had the lowest, while the "dysmorphism plus" category had the highest diagnostic yield. In our study, CMA proved to be a very useful method in the diagnosis of genetically caused congenital anomalies and neurodevelopmental disorders. DD/ID and dysmorphism stand out as important phenotypic features that significantly increase the diagnostic yield of the analysis.
Sections du résumé
BACKGROUND
BACKGROUND
Array-based genomic analysis is a gold standard for the detection of copy number variations (CNVs) as an important source of benign as well as pathogenic variations in humans. The introduction of chromosomal microarray (CMA) has led to a significant leap in diagnostics of genetically caused congenital malformations and neurodevelopmental disorders, with an average diagnostic yield of 15%. Here, we present our experience from a single laboratory perspective in four years' postnatal clinical CMA application.
METHODS
METHODS
DNA samples of 430 patients with congenital anomalies and/or neurodevelopmental disorders were analyzed by comparative genome hybridization using oligonucleotide-based microarray platforms. Interpretation of detected CNVs was performed according to current guidelines. The detection rate (DR) of clinically significant findings (pathogenic/likely pathogenic CNVs) was calculated for the whole cohort and isolated or combined phenotypic categories.
RESULTS
RESULTS
A total of 140 non-benign CNVs were detected in 113/430 patients (26.5%). In 70 patients at least one CNV was considered clinically significant thus reaching a diagnostic yield of 16.3%. The more complex the phenotype, including developmental delay/intellectual disability (DD/ID) as a prevailing feature, the higher the DR of clinically significant CNVs is obtained. Isolated congenital anomalies had the lowest, while the "dysmorphism plus" category had the highest diagnostic yield.
CONCLUSION
CONCLUSIONS
In our study, CMA proved to be a very useful method in the diagnosis of genetically caused congenital anomalies and neurodevelopmental disorders. DD/ID and dysmorphism stand out as important phenotypic features that significantly increase the diagnostic yield of the analysis.
Identifiants
pubmed: 35441737
doi: 10.1002/jcla.24441
pmc: PMC9169173
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e24441Subventions
Organisme : Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja
ID : 175091
Informations de copyright
© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.
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