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

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

JOURNAL=Frontiers in Neuroscience

VOLUME=17

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1165601

DOI=10.3389/fnins.2023.1165601

ISSN=1662-453X

ABSTRACT=<sec><title>Introduction</title><p>Genetic 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.</p></sec><sec><title>Methods</title><p>Whole-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.</p></sec><sec><title>Results</title><p>A gross intragenic deletion detected in <italic>MFSD8</italic> was investigated via gap-polymerase chain reaction (PCR), real-time quantitative PCR (qPCR), and mRNA sequence analysis. We identified 11 variants in seven genes (<italic>ALDH7A1, CDKL5, PCDH19, QARS1, POLG, GRIN2A</italic>, and <italic>MFSD8</italic>) responsible for genetic epilepsy in the seven families, respectively. A total of six variants (c.1408T&gt;G in <italic>ALDH7A1</italic>, c.1994_1997del in <italic>CDKL5</italic>, c.794G&gt;A in <italic>QARS1</italic>, c.2453C&gt;T in <italic>GRIN2A</italic>, and c.217dup and c.863+995_998+1480del in <italic>MFSD8</italic>) 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.</p></sec><sec><title>Methods</title><p>Based on the molecular findings, we have associated the intragenic deletion in <italic>MFSD8</italic> with the mutagenesis mechanism of <italic>Alu</italic>-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.</p></sec>