El Otmani Hicham, Tesson Christelle, Brice Alexis, Lesage Suzanne
Department of Neurology and Neurophysiology, Laboratory of Medical Genetics and Molecular Pathology and Laboratory of Cellular and Molecular Inflammatory, Degenerative and Oncologic Pathophysiology, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.
Department of Neurology and Neurophysiology, Ibn Rochd University Hospital, Casablanca, Morocco.
Mov Disord Clin Pract. 2025 May;12(5):648-652. doi: 10.1002/mdc3.14339. Epub 2025 Jan 23.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor symptoms, with a significant genetic component. Early-onset Parkinson's disease (EOPD), manifesting before age 45, is often linked to mutations in genes such as PARK2, PINK1, and PARK7, the latter coding for the protein DJ-1.
We present the first reported cases of EOPD carrying a previously undescribed homozygous PARK7 mutation, p.Thr110Pro.
Whole exom sequencing was performed on two inbred Moroccan siblings with early-onset Parkinson's disease (EOPD). Detailed clinical assessments, including neurological evaluations and cognitive testing, were conducted to understand the clinical presentation of the patients. Genetic analysis was also carried out to examine their genetic background. Therapeutic responses to treatments were monitored to assess the effectiveness of management strategies.
The sequencing revealed that both siblings carried the homozygous PARK7 mutation, p.Thr110Pro. Both siblings presented with typical EOPD features, including motor and non-motor symptoms. The patients both presented with cognitive impairment, with the male sibling exhibiting more pronounced symptoms. He also developed compulsive behaviors, which underscore the varied clinical presentations and therapeutic responses associated with this genetic variant.
This case study expands the genetic and geographic diversity of PD presentations, highlighting cognitive and behavioral challenges and variable therapeutic outcomes. It underscores the necessity for genetic screening and individualized management strategies for patients with PD.
帕金森病（PD）是一种进行性神经退行性疾病，其特征为运动和非运动症状，具有显著的遗传成分。早发性帕金森病（EOPD）在45岁之前发病，通常与PARK2、PINK1和PARK7等基因的突变有关，后者编码蛋白质DJ-1。
我们报告首例携带此前未描述的纯合PARK7突变p.Thr110Pro的早发性帕金森病病例。
对两名患有早发性帕金森病（EOPD）的近亲摩洛哥兄弟姐妹进行了全外显子组测序。进行了详细的临床评估，包括神经学评估和认知测试，以了解患者的临床表现。还进行了基因分析以检查他们的遗传背景。监测对治疗的反应以评估管理策略的有效性。
测序显示，这两名兄弟姐妹均携带纯合PARK7突变p.Thr110Pro。两名兄弟姐妹均表现出典型的早发性帕金森病特征，包括运动和非运动症状。两名患者均出现认知障碍，男性兄弟姐妹的症状更为明显。他还出现了强迫行为，这突出了与该基因变异相关的不同临床表现和治疗反应。
本病例研究扩展了帕金森病表现的遗传和地理多样性，突出了认知和行为挑战以及可变的治疗结果。它强调了对帕金森病患者进行基因筛查和个体化管理策略的必要性。
