Wan Yalan, Jiang Yanyan, Xie Zhiying, Ling Chen, Du Kang, Li Ran, Yuan Yun, Wang Zhaoxia, Sun Wei, Jin Haiqiang
Department of Neurology, Peking University First Hospital, Beijing, China.
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Neurol. 2022 Jul 13;13:922528. doi: 10.3389/fneur.2022.922528. eCollection 2022.
-associated neurodegeneration (PLAN) is a heterogeneous group of neurodegenerative diseases caused by biallelic mutations, covering diseases such as infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD), dystonia parkinsonism (DP), and autosomal recessive early-onset parkinsonism (AREP). The study aims to report the clinical and genetic features of a series of PLAN patients.
The clinical and radiological findings of five Chinese patients from three families were collected. Whole-exome next generation sequencing (NGS) was applied to identify the genetic causes. Co-segregation analysis of the detected candidate variants were performed in their families. The pathogenicity of identified novel variants was predicted by analysis.
NGS revealed compound heterozygous variants of gene in all five patients. There were six variants identified, including two known variants (c.116G>A, c.238G>A) and four novel variants (c.2120dupA, c.2071C>G, c.967G>A, c1534T>A). ACMG predicts c.2120dupA to be pathogenic, c.2071C>G and c.1534T>A to be likely pathogenic, and c1534T>A to be of uncertain significance. Clinically, four patients fell into the diagnosis of ANAD, and 1 into the diagnosis of AREP. Brain imaging revealed cerebellar atrophy, iron deposition in bilateral globus pallidus, and substantia nigra in three cases.
Four novel pathogenic variants were discovered and the pathogenic variant spectrum of the gene was expanded.
双等位基因突变导致的相关神经退行性疾病（PLAN）是一组异质性神经退行性疾病，涵盖婴儿型神经轴索性营养不良（INAD）、非典型神经轴索性营养不良（ANAD）、肌张力障碍帕金森综合征（DP）和常染色体隐性早发性帕金森病（AREP）等疾病。本研究旨在报告一系列PLAN患者的临床和遗传特征。
收集了来自三个家庭的五名中国患者的临床和影像学检查结果。应用全外显子组二代测序（NGS）来确定遗传病因。对检测到的候选变异在其家族中进行共分离分析。通过分析预测已鉴定的新变异的致病性。
NGS显示所有五名患者均存在该基因的复合杂合变异。共鉴定出六个变异，包括两个已知变异（c.116G>A，c.238G>A）和四个新变异（c.2120dupA，c.2071C>G，c.967G>A，c1534T>A）。ACMG预测c.2120dupA为致病性变异，c.2071C>G和c.1534T>A为可能致病性变异，c1534T>A意义不明确。临床上，四名患者被诊断为ANAD，一名患者被诊断为AREP。脑部影像学检查显示三例患者存在小脑萎缩、双侧苍白球和黑质铁沉积。
发现了四个新的致病性变异，扩展了该基因的致病性变异谱。
