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

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 cli...

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Autores principales: Cheng, Hao-Ling, Chen, Yi-Jun, Xue, Yan-Yan, Wu, Zhi-Ying, Li, Hong-Fu, Wang, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138368/
https://www.ncbi.nlm.nih.gov/pubmed/35624904
http://dx.doi.org/10.3390/brainsci12050517
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author Cheng, Hao-Ling
Chen, Yi-Jun
Xue, Yan-Yan
Wu, Zhi-Ying
Li, Hong-Fu
Wang, Ning
author_facet Cheng, Hao-Ling
Chen, Yi-Jun
Xue, Yan-Yan
Wu, Zhi-Ying
Li, Hong-Fu
Wang, Ning
author_sort Cheng, Hao-Ling
collection PubMed
description 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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spelling pubmed-91383682022-05-28 Clinical Characterization and Founder Effect Analysis in Chinese Patients with Phospholipase A2-Associated Neurodegeneration Cheng, Hao-Ling Chen, Yi-Jun Xue, Yan-Yan Wu, Zhi-Ying Li, Hong-Fu Wang, Ning Brain Sci Article 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. MDPI 2022-04-19 /pmc/articles/PMC9138368/ /pubmed/35624904 http://dx.doi.org/10.3390/brainsci12050517 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cheng, Hao-Ling
Chen, Yi-Jun
Xue, Yan-Yan
Wu, Zhi-Ying
Li, Hong-Fu
Wang, Ning
Clinical Characterization and Founder Effect Analysis in Chinese Patients with Phospholipase A2-Associated Neurodegeneration
title Clinical Characterization and Founder Effect Analysis in Chinese Patients with Phospholipase A2-Associated Neurodegeneration
title_full Clinical Characterization and Founder Effect Analysis in Chinese Patients with Phospholipase A2-Associated Neurodegeneration
title_fullStr Clinical Characterization and Founder Effect Analysis in Chinese Patients with Phospholipase A2-Associated Neurodegeneration
title_full_unstemmed Clinical Characterization and Founder Effect Analysis in Chinese Patients with Phospholipase A2-Associated Neurodegeneration
title_short Clinical Characterization and Founder Effect Analysis in Chinese Patients with Phospholipase A2-Associated Neurodegeneration
title_sort clinical characterization and founder effect analysis in chinese patients with phospholipase a2-associated neurodegeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138368/
https://www.ncbi.nlm.nih.gov/pubmed/35624904
http://dx.doi.org/10.3390/brainsci12050517
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