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https://doi.org/10.3325/cmj.2017.58.231
Chromosomal microarray in clinical diagnosis: a study of 337 patients with congenital anomalies and developmental delays or intellectual disability
Ivona Sansovi
; Department of Medical Genetics and Reproductive Health, Children
Ana-Maria Ivankov
; Department of Medical Genetics and Reproductive Health, Children
Adriana Bobinec
; Department of Medical Genetics and Reproductive Health, Children
Mijana Kero
; Department of Medical Genetics and Reproductive Health, Children
Ingeborg Barii
; Department of Medical Genetics and Reproductive Health, Children
Abstract
AimTo determine the diagnostic yield and criteria that could help to classify and interpret the copy number variations (CNVs) detected by chromosomal microarray (CMA) technique in patients with congenital and developmental abnormalities including dysmorphia, developmental delay (DD) or intellectual disability (ID), autism spectrum disorders (ASD) and congenital anomalies (CA). MethodCMA analysis was performed in 337 patients with DD/ID with or without dysmorphism, ASD, and/or CA. In 30 of 337 patients, chromosomal imbalances had previously been detected by classical cytogenetic and molecular cytogenetic methods. ResultsIn 73 of 337 patients, clinically relevant variants were detected and better characterized. Most of them were >1 Mb. Variants of unknown clinical significance (VOUS) were discovered in 35 patients. The most common VOUS size category was <300 kb (40.5%). Deletions and de novo imbalances were more frequent in pathogenic CNV than in VOUS category. CMA had a high diagnostic yield of 43/307, excluding patients previously detected by other methods. ConclusionCMA was valuable in establishing the diagnosis in a high proportion of patients. Criteria for classification and interpretation of CNVs include CNV size and type, mode of inheritance, and genotype-phenotype correlation. Agilent ISCA v2 Human Genome 8x60 K oligonucleotide microarray format proved to be reasonable resolution for clinical use, particularly in the regions that are recommended by the International Standard Cytogenomic Array (ISCA) Consortium and associated with well-established syndromes.
Keywords
Hrčak ID:
183993
URI
Publication date:
7.7.2017.
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