Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1784714607983591424 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9138368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT chenghaoling clinicalcharacterizationandfoundereffectanalysisinchinesepatientswithphospholipasea2associatedneurodegeneration AT chenyijun clinicalcharacterizationandfoundereffectanalysisinchinesepatientswithphospholipasea2associatedneurodegeneration AT xueyanyan clinicalcharacterizationandfoundereffectanalysisinchinesepatientswithphospholipasea2associatedneurodegeneration AT wuzhiying clinicalcharacterizationandfoundereffectanalysisinchinesepatientswithphospholipasea2associatedneurodegeneration AT lihongfu clinicalcharacterizationandfoundereffectanalysisinchinesepatientswithphospholipasea2associatedneurodegeneration AT wangning clinicalcharacterizationandfoundereffectanalysisinchinesepatientswithphospholipasea2associatedneurodegeneration |