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Clinical Implementation of Targeted Gene Sequencing for Malformation of Cortical Development

 Sangbo Lee  ;  Se Hee Kim  ;  Borahm Kim  ;  Seung-Tae Lee  ;  Jong Rak Choi  ;  Heung Dong Kim  ;  Joon Soo Lee  ;  Hoon-Chul Kang 
 PEDIATRIC NEUROLOGY, Vol.103 : 27-34, 2020 
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Issue Date
Epilepsy ; Gene panel ; Malformation of cortical development (MCD) ; Next-generation sequencing (NGS)
BACKGROUND: Malformations of cortical development comprise phenotypically heterogeneous conditions, and the diagnostic value of genetic testing in blood still remains to be elucidated. We used targeted gene sequencing to identify malformations of cortical development caused by germline mutations and characteristics associated with pathogenic mutations.

METHODS: A total of 81 patients with malformations of cortical development were included. Genomic DNA was isolated from peripheral blood. Ninety-six genes were assessed using a targeted next-generation sequencing panel. Single-nucleotide variants and exonic and chromosomal copy number variations were examined with our customized pipeline.

RESULTS: Genetic causes were identified from blood in 19 (23.5%) patients with malformations of cortical development; 14 patients had pathogenic or likely pathogenic single-nucleotide variants in seven genes, including DCX (n = 5), DEPDC5 (n = 2), PAFAH1B1 (n = 3), TUBA1A (n = 1), TUBA8 (n = 1), TUBB2B (n = 1), and TUBB3 (n = 1). Five patients had pathogenic copy number variations. Multifocal involvement of the lesion (tangential distribution, P < 0.001) and concurrent involvement of multiple structures such as the cortex, white matter, and ventricle (radial distribution, P = 0.003) were more commonly found in patients with identified genetic causes. Intellectual disability was also more commonly associated with pathogenic mutations (P = 0.048). In a multivariable regression analysis, both tangential and radial radiological distribution of malformations of cortical development were independently associated with positive germline test results.

CONCLUSION: We identified germline mutations in almost one-fourth of our patients with malformations of cortical development by using targeted gene sequencing. Germline abnormalities were more likely found in patients who had multifocal malformations of cortical development.
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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hoon Chul(강훈철) ORCID logo https://orcid.org/0000-0002-3659-8847
Kim, Borahm(김보람) ORCID logo https://orcid.org/0000-0003-0923-7744
Kim, Se Hee(김세희) ORCID logo https://orcid.org/0000-0001-7773-1942
Kim, Heung Dong(김흥동) ORCID logo https://orcid.org/0000-0002-8031-7336
Lee, Seung-Tae(이승태) ORCID logo https://orcid.org/0000-0003-1047-1415
Lee, Joon Soo(이준수) ORCID logo https://orcid.org/0000-0001-9036-9343
Choi, Jong Rak(최종락) ORCID logo https://orcid.org/0000-0002-0608-2989
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