Abstract
Genomic imbalances are the most common cause of congenital anomalies (CA) and intellectual disability (ID). The aims of this study were to identify copy number variations (CNVs) in 416 patients with CA and ID from 5 different genetics centers within 4 different states by using the Multiplex Ligation-dependent Probe Amplification (MLPA) technique and to apply the chromosomal microarray (CMA) methodology in selected cases. The samples were analyzed by MLPA kits P064, P036, P070 and P250. Positive results were found in 97/416 (23.3%) patients. CMA was applied in 14 selected cases. In 6/14 (42.85%) patients, CMA detected other copy number variations not detected by the MLPA studies. Although CMA is indispensable for genotype refinement, the technique is still unfeasible in some countries as a routine analysis due to economic and technical limitations. In these cases, clinical evaluation followed by karyotyping and MLPA analysis is a helpful and affordable solution for diagnostic purposes.
Highlights
copy number variations (CNVs) are defined as DNA fragments larger than one kilobase (1 Kb), with a distinct number of copies in the genome[2]
In order to determine the presence of CNVs in Brazilian patients with congenital anomalies (CA), intellectual disability (ID) and/or neurodevelopmental delay whose peripheral blood G-banding karyotyping had normal results, we used a combination of Multiplex Ligation Probe-dependent Amplification (MLPA) kits, and chromosomal microarray (CMA) was applied only in selected cases
Microdeletion 7q11.23 (Williams-Beuren syndrome) was identified in 20 patients, microdeletion 1p36 was identified in 6 patients, and microdeletion 4p16.3 (Wolf-Hirschhorn syndrome) was identified in 5 patients
Summary
CNVs are defined as DNA fragments larger than one kilobase (1 Kb), with a distinct number of copies in the genome[2]. Until the advent of molecular techniques such as fluorescent in situ hybridization (FISH), polymerase chain reaction (PCR), Multiplex Ligation Probe-dependent Amplification (MLPA), and chromosomal microarray (CMA), small CNVs were not detected[8]. Consistent with this fact, the literature has shown a higher diagnostic usage of cytogenomic techniques over G-band karyotyping in patients with CA and ID9, with a 9–30% detection by MLPA, depending on the combination of kits and previous screening[10,11], and 20% by chromosomal microarray (CMAs)[12] versus 5% with G-band karyotyping. We evaluated the efficiency and applicability of this cytogenomic approach in the investigation of a large series of patients undergoing clinical genetic follow-up
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