Frontiers in Neuroscience (May 2023)

Molecular analysis and prenatal diagnosis of seven Chinese families with genetic epilepsy

  • Bin Mao,
  • Bin Mao,
  • Na Lin,
  • Na Lin,
  • Danhua Guo,
  • Danhua Guo,
  • Deqin He,
  • Deqin He,
  • Huili Xue,
  • Huili Xue,
  • Lingji Chen,
  • Lingji Chen,
  • Qianqian He,
  • Qianqian He,
  • Min Zhang,
  • Min Zhang,
  • Meihuan Chen,
  • Meihuan Chen,
  • Hailong Huang,
  • Hailong Huang,
  • Liangpu Xu,
  • Liangpu Xu

DOI
https://doi.org/10.3389/fnins.2023.1165601
Journal volume & issue
Vol. 17

Abstract

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IntroductionGenetic epilepsy is a large group of clinically and genetically heterogeneous neurological disorders characterized by recurrent seizures, which have a clear association with genetic defects. In this study, we have recruited seven families from China with neurodevelopmental abnormalities in which epilepsy was a predominant manifestation, aiming to elucidate the underlying causes and make a precise diagnosis for the cases.MethodsWhole-exome sequencing (WES) combined with Sanger sequencing was used to identify the causative variants associated with the diseases in addition to essential imaging and biomedical examination.ResultsA gross intragenic deletion detected in MFSD8 was investigated via gap-polymerase chain reaction (PCR), real-time quantitative PCR (qPCR), and mRNA sequence analysis. We identified 11 variants in seven genes (ALDH7A1, CDKL5, PCDH19, QARS1, POLG, GRIN2A, and MFSD8) responsible for genetic epilepsy in the seven families, respectively. A total of six variants (c.1408T>G in ALDH7A1, c.1994_1997del in CDKL5, c.794G>A in QARS1, c.2453C>T in GRIN2A, and c.217dup and c.863+995_998+1480del in MFSD8) have not yet been reported to be associated with diseases and were all evaluated to be pathogenic or likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines.MethodsBased on the molecular findings, we have associated the intragenic deletion in MFSD8 with the mutagenesis mechanism of Alu-mediated genomic rearrangements for the first time and provided genetic counseling, medical suggestions, and prenatal diagnosis for the families. In conclusion, molecular diagnosis is crucial to obtain improved medical outcomes and recurrence risk evaluation for genetic epilepsy.

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