Clinical Characterization and Founder Effect Analysis in Chinese Patients with Phospholipase A2-Associated Neurodegeneration

被引:7
作者
Cheng, Hao-Ling [1 ]
Chen, Yi-Jun [1 ]
Xue, Yan-Yan [2 ]
Wu, Zhi-Ying [2 ]
Li, Hong-Fu [2 ]
Wang, Ning [1 ,3 ]
机构
[1] Fujian Med Univ, Inst Neurol, Dept Neurol, Affiliated Hosp 1, Fuzhou 350005, Peoples R China
[2] Zhejiang Univ, Affiliated Hosp Zhejiang Prov 2, Key Lab Med Neurobiol Zhejiang Prov, Dept Neurol,Res Ctr Neurol,Sch Med, Hangzhou 310000, Peoples R China
[3] Fujian Med Univ, Fujian Key Lab Mol Neurol, Fuzhou 350005, Peoples R China
基金
中国国家自然科学基金;
关键词
phospholipase A2-associated neurodegeneration; PLA2G6; clinical features; founder effect; Chinese; PLA2G6-ASSOCIATED NEURODEGENERATION; PLA2G6; MUTATIONS; HETEROGENEITY; DISORDERS; INFANTILE; VARIANTS; SPECTRUM; FAMILY;
D O I
10.3390/brainsci12050517
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
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页数:12
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