PDF(Pubmed)
Abstract：
BACKGROUND: The glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 (LRRK2) genes are associated with the risk of sporadic Parkinson\'s disease (PD). As an environmental factor, hypoxic insults may impair dopamine neurons in the substantia nigra and exacerbate PD symptoms. However, covariants of GBA and LRRK2 combined with hypoxic insults in clinical cases of Parkinsonism have not yet been reported.
METHODS: A 69-year-old male patient with PD and his relatives were clinically characterized and sequenced using the whole-exome technique. A novel covariant, c.1448 T > C (p. L483P, rs421016) on GBA and c.691 T > C (p. S231P, rs201332859) on LRRK2 were identified in this patient who first developed bradykinesia and rigidity in the neck at one month after an acute hypoxic insult during mountaineering. The patient presented with a mask-like face, festinating gait, asymmetric bradykinesia, and moderate rigidity. These symptoms were treated with levodopa and pramipexole, resulting in a 65% improvement in the Unified Parkinson\'s Disease Rating Scale (UPDRS) motor score. These parkinsonian symptoms persisted and developed with hallucinations, constipation, and rapid eye movement sleep behavior disorder. After 4 years, the patient exhibited a wearing-off phenomenon and died from pulmonary infection 8 years after disease onset. His parents, wife, and siblings were not diagnosed with PD, and his son carried p. L483P without Parkinsonism-like symptoms.
CONCLUSIONS: This is a case report of PD after hypoxic insult in a patient carrying a covariant of GBA and LRRK2. This study may help us understand the interaction between genetic and environmental factors in clinical PD.
METHODS: A 69-year-old male patient with PD and his relatives were clinically characterized and sequenced using the whole-exome technique. A novel covariant, c.1448 T > C (p. L483P, rs421016) on GBA and c.691 T > C (p. S231P, rs201332859) on LRRK2 were identified in this patient who first developed bradykinesia and rigidity in the neck at one month after an acute hypoxic insult during mountaineering. The patient presented with a mask-like face, festinating gait, asymmetric bradykinesia, and moderate rigidity. These symptoms were treated with levodopa and pramipexole, resulting in a 65% improvement in the Unified Parkinson\'s Disease Rating Scale (UPDRS) motor score. These parkinsonian symptoms persisted and developed with hallucinations, constipation, and rapid eye movement sleep behavior disorder. After 4 years, the patient exhibited a wearing-off phenomenon and died from pulmonary infection 8 years after disease onset. His parents, wife, and siblings were not diagnosed with PD, and his son carried p. L483P without Parkinsonism-like symptoms.
CONCLUSIONS: This is a case report of PD after hypoxic insult in a patient carrying a covariant of GBA and LRRK2. This study may help us understand the interaction between genetic and environmental factors in clinical PD.
摘要：
背景：葡萄糖脑苷脂酶（GBA）和富含亮氨酸重复序列激酶2（LRRK2）基因与散发性帕金森病（PD）的风险相关。作为环境因素,低氧损伤可能损害黑质中的多巴胺神经元并加剧PD症状。然而,尚未报道在帕金森病临床病例中GBA和LRRK2的共变体与缺氧损伤的联合。
方法：一名69岁男性PD患者及其亲属使用全外显子组技术进行临床特征和测序。一种新颖的协变，c.1448T>C（p。L483P,rs421016）在GBA和c.691T>C（p。S231P,在该患者中发现了LRRK2上的rs201332859），该患者在登山过程中急性缺氧后一个月首次出现运动迟缓和颈部僵硬。病人的脸像面具一样，迷人的步态，不对称运动迟缓，适度的刚性。这些症状用左旋多巴和普拉克索治疗，导致统一帕金森病评定量表(UPDRS)运动评分提高65%。这些帕金森病症状持续存在并伴随幻觉发展，便秘,和快速眼动睡眠行为障碍。四年后,患者在发病8年后出现耗损现象,死于肺部感染.他的父母,妻子,兄弟姐妹没有被诊断为PD,和他的儿子携带p。L483P没有帕金森病样症状。
结论：这是一例携带GBA和LRRK2共变的患者缺氧损伤后PD的病例报告。这项研究可能有助于我们了解临床PD中遗传和环境因素之间的相互作用。
方法：一名69岁男性PD患者及其亲属使用全外显子组技术进行临床特征和测序。一种新颖的协变，c.1448T>C（p。L483P,rs421016）在GBA和c.691T>C（p。S231P,在该患者中发现了LRRK2上的rs201332859），该患者在登山过程中急性缺氧后一个月首次出现运动迟缓和颈部僵硬。病人的脸像面具一样，迷人的步态，不对称运动迟缓，适度的刚性。这些症状用左旋多巴和普拉克索治疗，导致统一帕金森病评定量表(UPDRS)运动评分提高65%。这些帕金森病症状持续存在并伴随幻觉发展，便秘,和快速眼动睡眠行为障碍。四年后,患者在发病8年后出现耗损现象,死于肺部感染.他的父母,妻子,兄弟姐妹没有被诊断为PD,和他的儿子携带p。L483P没有帕金森病样症状。
结论：这是一例携带GBA和LRRK2共变的患者缺氧损伤后PD的病例报告。这项研究可能有助于我们了解临床PD中遗传和环境因素之间的相互作用。
