Details

Autor(en) / Beteiligte

• Tian, Mao‐Qiang
• Liu, Xiao‐Rong
• Lin, Si‐Mei
• Wang, Jie
• Luo, Sheng
• Gao, Liang‐Di
• Chen, Xiao‐Bin
• Liang, Xiao‐Yu
• Liu, Zhi‐Gang
• He, Na
• Yi, Yong‐Hong
• Liao, Wei‐Ping

Titel

Variants in BRWD3 associated with X‐linked partial epilepsy without intellectual disability

Ist Teil von

• CNS neuroscience & therapeutics, 2023-02, Vol.29 (2), p.727-735

Ort / Verlag

England: John Wiley & Sons, Inc

Erscheinungsjahr

2023

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Aims Etiology of the majority patients with idiopathic partial epilepsy (IPE) remains elusive. We thus screened the potential disease‐associated variants in the patients with IPE. Methods Trios‐based whole exome sequencing was performed in a cohort of 320 patients with IPE. Frequency and molecular effects of variants were predicted. Results Three novel BRWD3 variants were identified in five unrelated cases with IPE, which were four male cases and one female case. The variants included two recurrent missense variants (c.836C>T/p.Thr279Ile and c.4234A>C/p.Ile1412Leu) and one intronic variant close to splice site (c.2475 + 6A>G). The two missense variants were located in WD40 repeat domain and bromodomain, respectively. They were predicted to be damaging by silico tools and change hydrogen bonds with surrounding amino acids. The frequency of mutant alleles in this cohort was significantly higher than that in the controls of East Asian and all population of gnomAD. All these variants were inherited from the asymptomatic mothers. Four male cases presented frequent seizures at onset, while the female case only had two fever‐triggered seizures. They showed good responses to valproate and lamotrigine, then finally became seizure free. All the cases had no intellectual disability. Further analysis demonstrated that all previously reported destructive variants of BRWD3 caused intellectual disability, while missense variants located in WD40 repeat domains and bromodomains of BRWD3 were associated with epilepsy. Conclusion BRWD3 gene is potentially associated with X‐linked partial epilepsy without intellectual disability. The genotypes and locations of BRWD3 variants may explain for their phenotypic variation. This study reports three novel variants of BRWD3 in five unrelated cases with partial epilepsy and without mental retardation and demonstrates that the BRWD3 gene is potentially a candidate pathogenic gene of epilepsy. The genotypes and locations of BRWD3 variants may explain for their phenotypic variation.