El Mouhi Hinde, Elmakhzen Badreddine, Bouyahyaoui Amina, Hida Mustapha, Ouldim Karim, Bouguenouch Laila, Chaouki Sana
Laboratory of Biomedical and Translational Research, Sidi Mohamed Ben Abdellah University Faculty of Medicine and Pharmacy, Fez, Morocco.
Engineering Science and Technology Doctoral Study Center, Faculty of Sciences and Technologies, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
BMJ Neurol Open. 2025 Sep 21;7(2):e001267. doi: 10.1136/bmjno-2025-001267. eCollection 2025.
Epilepsy-related ligand-receptor complex, leucine-rich glioma-inactivated 1 ()a disintegrin and metalloproteinase 22 (), regulates neuronal excitability and synaptic transmission and has emerged as a determinant of brain excitability. Epilepsy-related variants have been described in both and genes. A partial epilepsy, autosomal dominant lateral temporal epilepsy (ADLTE) is caused by an heterozygous variant. A recessive developmental and epileptic encephalopathy with infantile onset is due to homozygous inactivating variants.
We present the case of Moroccan siblings with epileptic encephalopathy due to a homozygous variant within the gene previously unreported in the homozygous state.
We performed whole-exome sequencing and family segregation analysis to identify and confirm the genetic cause of the condition in the affected siblings.
The clinical features mimic related developmental and epileptic encephalopathy rather than the typical -associated autosomal dominant lateral temporal epilepsy. Family segregation analysis demonstrated variable expressivity, with asymptomatic carrier parents and a cousin with focal temporal epilepsy carrying the variant in the heterozygous state.
This case highlights a homozygous variant previously unreported in the homozygous state, leading to a clinical presentation more reminiscent of -related pathology rather than the classical ADLTE, expanding our understanding of -associated conditions.
癫痫相关配体-受体复合物，富含亮氨酸的胶质瘤失活1（LRG1）和去整合素金属蛋白酶22（ADAM22），调节神经元兴奋性和突触传递，并已成为脑兴奋性的一个决定因素。在LRG1和ADAM22基因中均已描述了与癫痫相关的变异。一种部分性癫痫，常染色体显性外侧颞叶癫痫（ADLTE）由LRG1杂合变异引起。一种隐性起病于婴儿期的发育性和癫痫性脑病是由于LRG1纯合失活变异所致。
我们报告一例摩洛哥兄弟姐妹因LRG1基因纯合变异导致癫痫性脑病的病例，该变异在纯合状态下此前未见报道。
我们进行了全外显子组测序和家系分离分析，以识别并确认患病兄弟姐妹病情的遗传原因。
临床特征类似于相关的发育性和癫痫性脑病，而非典型的LRG1相关常染色体显性外侧颞叶癫痫。家系分离分析显示存在可变表达，无症状的携带者父母以及一名患有局灶性颞叶癫痫的表亲为该变异的杂合携带者。
该病例突出了一种此前未见纯合状态报道的LRG1纯合变异，导致的临床表现更让人联想到与ADAM22相关的病理改变，而非经典的ADLTE，扩展了我们对LRG1相关疾病的认识。
