Despite the great advances achieved in clinical genetics thanks to the incorporation of NGS (Next Generation Sequencing), a significant percentage of patients with diseases of genetic origin still do not have a conclusive molecular diagnosis. The incorporation of state-of-the-art bioinformatic methods has allowed the implementation of CNVs (Copy Number Variants) detection in NGS analysis, improving its diagnostic efficiency. In this study, the clinical utility of the detection of CNVs by NGS has been proven.
During 2018, 275 patients were studied using the NGS technique without obtaining an accurate genetic diagnosis. Bioinformatic tools that compare the normalized sequencing depth between patients and controls were used to determine CNVs. The results obtained were compared with patients own laboratory database and controls to rule out polymorphisms and false positives. All causal CNVs were confirmed by MLPA.
Pathogenic CNVs causing the disease were detected in 11 of the 275 patients (4%). Specifically, CNVs were detected for pathologies with autosomal dominant inheritance patterns (TSC2, MSH2, and FBN1), as well as for genes with autosomal recessive inheritance patterns, including two homozygous deletions (KCNV2 and RDX) and one heterozygous deletion with an SNV (Single Nucleotide Variant) in the PKHD1 gene. One of the most notable cases corresponds to a patient suspected of hypomagnesemia in which two deletions were identified in compound heterozygous mutation in the TRPM6 gene.
About the Presenter
Albert Ferran finished his MSc in Genetic Anthropology in 2011 and worked as a research scientist at The University of Barcelona and The Mar Institute of Medical Research (IMIM). Because of his work, he has authored different publications in genetics. During the last 4 years, Albert has worked as an Analyst and Bioinformatician at Reference Laboratory, a Spanish laboratory specialised in clinical analysis and genetics. He has analysed hundreds of clinical cases, through the study of NGS data, helping to diagnose most of the cases. He is specialised in analysis of CNVs. Currently, he is finishing his MSc in Bioinformatics and Biostatistics at The Open University of Catalonia.