{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T15:51:15Z","timestamp":1773503475980,"version":"3.50.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071306"],"award-info":[{"award-number":["82071306"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>PLA2G6<\/jats:italic>-associated neurodegeneration (PLAN) is a heterogeneous group of neurodegenerative diseases caused by biallelic <jats:italic>PLA2G6<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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 <jats:italic>in silico<\/jats:italic> analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NGS revealed compound heterozygous variants of <jats:italic>PLA2G6<\/jats:italic> gene in all five patients. There were six <jats:italic>PLA2G6<\/jats:italic> variants identified, including two known variants (c.116G&amp;gt;A, c.238G&amp;gt;A) and four novel variants (c.2120dupA, c.2071C&amp;gt;G, c.967G&amp;gt;A, c1534T&amp;gt;A). ACMG predicts c.2120dupA to be pathogenic, c.2071C&amp;gt;G and c.1534T&amp;gt;A to be likely pathogenic, and c1534T&amp;gt;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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Four novel pathogenic variants were discovered and the pathogenic variant spectrum of the <jats:italic>PLA2G6<\/jats:italic> gene was expanded.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.922528","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T12:35:17Z","timestamp":1657715717000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Novel PLA2G6 Pathogenic Variants in Chinese Patients With PLA2G6-Associated 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