Research Laboratory 'NeuroPédiatrie' (LR19ES15), Sfax Medical School, Sfax University, Sfax, Tunisia.
Laboratory of Molecular and Functional Genetics, Faculty of Science of Sfax, Sfax University, Sfax, Tunisia.
Orphanet J Rare Dis. 2021 Jul 17;16(1):317. doi: 10.1186/s13023-021-01951-w.
Developmental and epileptic encephalopathies (DEE) are chronic neurological conditions where epileptic activity contributes to the progressive disruption of brain function, frequently leading to impaired motor, cognitive and sensory development.
The present study reports a clinical investigation and a molecular analysis by Next Generation Sequencing (NGS) of a large consanguineous family comprising several cases of developmental and epileptic encephalopathy. Bioinformatic prediction and molecular docking analysis were also carried out.
The majority of patients in our studied family had severe developmental impairments, early-onset seizures, brain malformations such as cortical atrophy and microcephaly, developmental delays and intellectual disabilities. The molecular investigations revealed a novel homozygous variant c.1411G>A (p.Gly471Arg) in the GRM7 gene which was segregating with the disease in the family. Bioinformatic tools predicted its pathogenicity and docking analysis revealed its potential effects on mGlu7 protein binding to its ligand.
Our results contribute to a better understanding of the impact of GRM7 variants for the newly described associated phenotype.
发育性和癫痫性脑病（DEE）是一种慢性神经疾病，其癫痫活动导致大脑功能进行性紊乱，常导致运动、认知和感觉发育受损。
本研究报告了一项临床研究和下一代测序（NGS）的分子分析，该研究涉及一个大型近亲家族，其中包括几例发育性和癫痫性脑病患者。还进行了生物信息学预测和分子对接分析。
我们研究的家族中的大多数患者均存在严重的发育障碍、早发性癫痫、脑畸形（如皮质萎缩和小头畸形）、发育迟缓以及智力障碍。分子研究发现 GRM7 基因中的一个新的纯合变异 c.1411G>A（p.Gly471Arg），该变异在家族中与疾病共分离。生物信息学工具预测其致病性，对接分析显示其可能影响 mGlu7 蛋白与其配体的结合。
我们的研究结果有助于更好地理解 GRM7 变异对新描述的相关表型的影响。
