Cheng Hao-Ling, Chen Yi-Jun, Xue Yan-Yan, Wu Zhi-Ying, Li Hong-Fu, Wang Ning
Department of Neurology, Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
Research Center of Neurology, Key Laboratory of Medical Neurobiology of Zhejiang Province, Department of Neurology, Second Affiliated Hospital of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310000, China.
Brain Sci. 2022 Apr 19;12(5):517. doi: 10.3390/brainsci12050517.
PLA2G6-associated neurodegeneration (PLAN) is a rare autosomal recessive disorder caused by PLA2G6 mutations. This study aimed to investigate the clinical characteristics and mutation spectrum of PLAN and to investigate the founder effects in Chinese PLAN patients. Six Chinese PLAN families were clinically examined in detail and whole-exome sequencing was performed in the probands. Haplotype analysis was performed in five families with the PLA2G6 c.991G > T mutation using 23 single nucleotide polymorphism markers. Furthermore, all previously reported PLA2G6 mutations and patients in China were reviewed to summarize the genetic and clinical features of PLAN. Interestingly, we found that one patient had hereditary spastic paraplegia and showed various atypical clinical characteristics of PLAN, and five patients had a phenotype of parkinsonism. All probands were compound heterozygotes for PLA2G6 variants, including four novel pathogenic/likely pathogenic mutations (c.967G > A, c.1450G > T, c.1631T > C, and c.1915delG) and five known pathogenic mutations. Haplotype analyses revealed that patients carrying PLA2G6 c.991G > T mutations shared a haplotype of 717 kb. The frequencies of psychiatric features, cognitive decline, and myoclonus in Chinese patients with PLA2G6-related parkinsonism were significantly different from those in European patients. Thus, our study expands the clinical and genetic spectrum of PLAN and provides an insightful view of the founder effect to better diagnose and understand the disease.
磷脂酶A2G6相关神经退行性变（PLAN）是一种由PLA2G6突变引起的罕见常染色体隐性疾病。本研究旨在调查PLAN的临床特征和突变谱，并研究中国PLAN患者中的奠基者效应。对6个中国PLAN家系进行了详细的临床检查，并对先证者进行了全外显子测序。使用23个单核苷酸多态性标记对5个携带PLA2G6 c.991G>T突变的家系进行了单倍型分析。此外，对中国所有先前报道的PLA2G6突变和患者进行了回顾，以总结PLAN的遗传和临床特征。有趣的是，我们发现1例患者患有遗传性痉挛性截瘫，并表现出PLAN的各种非典型临床特征，5例患者具有帕金森综合征的表型。所有先证者均为PLA2G6变异的复合杂合子，包括4个新的致病/可能致病突变（c.967G>A、c.1450G>T、c.1631T>C和c.1915delG）和5个已知的致病突变。单倍型分析显示，携带PLA2G6 c.991G>T突变的患者共享一个717 kb的单倍型。中国PLA2G6相关帕金森综合征患者的精神症状、认知衰退和肌阵挛的发生率与欧洲患者有显著差异。因此，我们的研究扩展了PLAN的临床和遗传谱，并为更好地诊断和理解该疾病的奠基者效应提供了深刻见解。
