The clinical utility of targeted NGS in neurodevelopmental disorders: a case of a girl with pontocerebellar hypoplasia caused by TSEN54 gene pathogenic variants

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Authors

WAYHELOVÁ Markéta VALLOVÁ Vladimíra HLADÍLKOVÁ Eva FILKOVÁ Hana OPPELT Jan ŠOUKALOVÁ Jana KUGLÍK Petr

Year of publication 2020
Type Conference abstract
MU Faculty or unit

Faculty of Science

Citation
Description Next-generation sequencing (NGS) techniques have become a powerful tool for the identification of the genetic causes of the heterogeneous conditions such as intellectual disabilities, multiple congenital anomalies and autism spectrum disorders. Here we present our first experience with targeted NGS approach using commercially available design SureSelect Inherited Disease (Agilent Technologies, Santa Clara, CA, USA) containing more than 2700 genes known to cause inherited disorders. We report on a case of 9-year-old boy with a diagnosis of severe intellectual disability related to early myoclonic encephalopathy. This patient was examined according to our investigatory algorithm, from G-banding karyotype (46,XY) to array-CGH on oligonucleotide DNA microarrays (Agilent Technologies, Santa Clara, CA, USA) followed by confirmative targeted quantitative PCR and FISH. We detected a de novo copy-number gain of 18q21.23 (539 kb), however, it could not explain his pathological phenotype. Consequently this patient was included in our pilot study using targeted NGS with pre-designed gene panel SureSelect Inherited disease and Illumina MiSeq. We detected de novo heterozygous missense genetic variant in SCN2A gene, resulting in the amino acid residue change from alanine to valine at position 263 (p.Ala263Val). This variant had been previously described as definitely pathogenic in patients with Otahara syndrome. This case has proved the usefulness and effectivity of our molecular diagnostics algorithm enhanced by NGS approaches leading to higher diagnostic yield of heterogeneous genetic conditions. This study was supported by IP 2016 (University Hospital, Brno) and the Specific Research Fund (Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno).
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