Epilepsy Combined With Multiple Gene Heterozygous Mutation

Frontiers in Pediatrics

Wen Qi¹  He Qiuju¹  Li Zhifa³  Sun Xiaofang⁴  Xie Yingjun⁴  Wang Ding⁴  Zhuang Jianlong⁵ 

[1] Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, China;Department of Obstetrics and Gynaecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;Gastrointestinal Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;Prenatal Diagnosis Center, Quanzhou Women's and Children's Hospital, Quanzhou, China;

关键词: whole exome sequencing;    Sanger sequencing;    epilepsy;    coexpression analysis;    heterozygous mutations;   

DOI  :  10.3389/fped.2022.763642

来源: DOAJ

【 摘 要 】

The fast pace of gene discovery has resulted in groundbreaking advances in the field of epilepsy genetics. Clinical testing using comprehensive gene panels, exomes, or genomes is now increasingly available and has significantly increased the diagnostic yield for early-onset epilepsies and enabled precision medicine approaches. In this paper, we report a case of epilepsy in a pedigree. The proband had heterozygous mutations in KCNC1 (NM_001112741.1:c.959G>A, p. Arg320His), CAPN3 (NM_000070.2:c.526G>A, p. Val176Met), and NEFH (NM_021076.3:c. 2595 delC, p. Lys866Argfs*51). Sanger sequencing verification was consistent with the results of whole-exome sequencing. The KCNC1 mutation was a de novo mutation, and the CAPN3 and NEFH mutations were inherited from their father and mother, respectively. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, a heterozygous mutation was found for APOB (NM_000384.2: c.10579C > T, p. Arg3527Trp). The heterozygous mutation at this site was inherent in the pedigree. Coexpression analysis indicated that heterozygous mutations of KCNC1, CAPN3, NEFH, and APOB were closely related to the clinical phenotypes of the patient, and the clinical phenotypic heterogeneity of the disease may be the result of the interaction of multiple genes.

【 授权许可】

Unknown