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

WAYHELOVÁ, Markéta, Vladimíra VALLOVÁ, Eva HLADÍLKOVÁ, Hana FILKOVÁ, Jan OPPELT, Jana ŠOUKALOVÁ and Petr KUGLÍK. The clinical utility of targeted NGS in neurodevelopmental disorders: a case of a girl with pontocerebellar hypoplasia caused by TSEN54 gene pathogenic variants. In ESHG 2020 - European Human Genetics Virtual Conference. 2020. ISSN 1018-4813.

Basic information

• Original name: The clinical utility of targeted NGS in neurodevelopmental disorders: a case of a girl with pontocerebellar hypoplasia caused by TSEN54 gene pathogenic variants
• Authors: WAYHELOVÁ, Markéta (203 Czech Republic, belonging to the institution), Vladimíra VALLOVÁ (703 Slovakia), Eva HLADÍLKOVÁ (203 Czech Republic, belonging to the institution), Hana FILKOVÁ (203 Czech Republic, belonging to the institution), Jan OPPELT (203 Czech Republic, belonging to the institution), Jana ŠOUKALOVÁ (203 Czech Republic, belonging to the institution) and Petr KUGLÍK (203 Czech Republic, guarantor, belonging to the institution).
• Edition: ESHG 2020 - European Human Genetics Virtual Conference, 2020.

Other information

• Original language: English
• Type of outcome: Conference abstract
• Field of Study: 10603 Genetics and heredity
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 4.246
• RIV identification code: RIV/00216224:14310/20:00116860
• Organization unit: Faculty of Science
• ISSN: 1018-4813
• UT WoS: 000598482603153
• Keywords in English: neurodevelopmental disorders; NGS

Abstract

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).

Links

• MUNI/A/1127/2019, interní kód MU: Name: Podpora výzkumné činnosti studentů molekulární biologie a genetiky 8 (Acronym: MBG 8)

Investor: Masaryk University, Category A