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Novel PLA2G6 Pathogenic Variants in Chinese Patients With PLA2G6-Associated Neurodegeneration

BACKGROUND: PLA2G6-associated neurodegeneration (PLAN) is a heterogeneous group of neurodegenerative diseases caused by biallelic PLA2G6 mutations, covering diseases such as infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD), dystonia parkinsonism (DP), and autosomal reces...

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Autores principales: Wan, Yalan, Jiang, Yanyan, Xie, Zhiying, Ling, Chen, Du, Kang, Li, Ran, Yuan, Yun, Wang, Zhaoxia, Sun, Wei, Jin, Haiqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327523/
https://www.ncbi.nlm.nih.gov/pubmed/35911906
http://dx.doi.org/10.3389/fneur.2022.922528
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author Wan, Yalan
Jiang, Yanyan
Xie, Zhiying
Ling, Chen
Du, Kang
Li, Ran
Yuan, Yun
Wang, Zhaoxia
Sun, Wei
Jin, Haiqiang
author_facet Wan, Yalan
Jiang, Yanyan
Xie, Zhiying
Ling, Chen
Du, Kang
Li, Ran
Yuan, Yun
Wang, Zhaoxia
Sun, Wei
Jin, Haiqiang
author_sort Wan, Yalan
collection PubMed
description BACKGROUND: PLA2G6-associated neurodegeneration (PLAN) is a heterogeneous group of neurodegenerative diseases caused by biallelic PLA2G6 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. METHODS: 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 in silico analysis. RESULTS: NGS revealed compound heterozygous variants of PLA2G6 gene in all five patients. There were six PLA2G6 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. CONCLUSIONS: Four novel pathogenic variants were discovered and the pathogenic variant spectrum of the PLA2G6 gene was expanded.
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spelling pubmed-93275232022-07-28 Novel PLA2G6 Pathogenic Variants in Chinese Patients With PLA2G6-Associated Neurodegeneration Wan, Yalan Jiang, Yanyan Xie, Zhiying Ling, Chen Du, Kang Li, Ran Yuan, Yun Wang, Zhaoxia Sun, Wei Jin, Haiqiang Front Neurol Neurology BACKGROUND: PLA2G6-associated neurodegeneration (PLAN) is a heterogeneous group of neurodegenerative diseases caused by biallelic PLA2G6 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. METHODS: 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 in silico analysis. RESULTS: NGS revealed compound heterozygous variants of PLA2G6 gene in all five patients. There were six PLA2G6 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. CONCLUSIONS: Four novel pathogenic variants were discovered and the pathogenic variant spectrum of the PLA2G6 gene was expanded. Frontiers Media S.A. 2022-07-13 /pmc/articles/PMC9327523/ /pubmed/35911906 http://dx.doi.org/10.3389/fneur.2022.922528 Text en Copyright © 2022 Wan, Jiang, Xie, Ling, Du, Li, Yuan, Wang, Sun and Jin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Wan, Yalan
Jiang, Yanyan
Xie, Zhiying
Ling, Chen
Du, Kang
Li, Ran
Yuan, Yun
Wang, Zhaoxia
Sun, Wei
Jin, Haiqiang
Novel PLA2G6 Pathogenic Variants in Chinese Patients With PLA2G6-Associated Neurodegeneration
title Novel PLA2G6 Pathogenic Variants in Chinese Patients With PLA2G6-Associated Neurodegeneration
title_full Novel PLA2G6 Pathogenic Variants in Chinese Patients With PLA2G6-Associated Neurodegeneration
title_fullStr Novel PLA2G6 Pathogenic Variants in Chinese Patients With PLA2G6-Associated Neurodegeneration
title_full_unstemmed Novel PLA2G6 Pathogenic Variants in Chinese Patients With PLA2G6-Associated Neurodegeneration
title_short Novel PLA2G6 Pathogenic Variants in Chinese Patients With PLA2G6-Associated Neurodegeneration
title_sort novel pla2g6 pathogenic variants in chinese patients with pla2g6-associated neurodegeneration
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327523/
https://www.ncbi.nlm.nih.gov/pubmed/35911906
http://dx.doi.org/10.3389/fneur.2022.922528
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