119ae1165ecdb258cc1ff28fb72bfed5 322607.pdf 9718fa853f8a83e23f98be824cb2a341deb32920 322607.pdf 2476a92d2016a7be7d2b72a33a2f76d4917f1185ec44801f3b5ae50d785fbfea 322607.pdf Title: Genotype–Phenotype Relations for the Dystonia-Parkinsonism Genes GLB1, SLC6A3, SLC30A10, SLC39A14, and PLA2G6: MDSGene Systematic Review Subject: The Movement Disorders Society recommends the DYT/PARK prefix for genes where dystonia and parkinsonism are prominent in approximately half or more of patients. This systematic review explores the genotype–phenotype correlations of GLB1, SLC6A3, SLC30A10, PLA2G6, and SLC39A14—recently classified as DYT SLC39A14 and historically linked to dystonia-parkinsonism. We searched PubMed and the Human Gene Mutation Database using standardized terms, including English-language, peer-reviewed publications up to February 2024. Following the MDSGene protocol, we extracted individual-level data on patients with biallelic pathogenic variants and at least one movement disorder. Features were marked “missing” if not explicitly reported. Of 1828 articles, 128 were eligible. We identified 386 patients and 262 variants. The median age at onset was 3 years for GLB1, 3 months for SLC6A3, 2.5 years for SLC30A10, 1.5 years for SLC39A14, and 16 years for PLA2G6. Missing data may reflect underreporting of negative findings. Case reports/serie, may bias toward atypical presentations. Our analysis showed dystonia-parkinsonism predominates in SLC6A3 and PLA2G6, while GLB1, SLC30A10, and SLC39A1 show predominantly dystonic phenotypes with a low frequency of parkinsonism. Ataxia was common in GLB1 and PLA2G6. Awareness of these phenotypes is essential for early diagnosis and intervention, particularly in treatable conditions like SLC30A10 or SLC39A14. The predominantly dystonic phenotype in GLB1, SLC30A10, and SLC39A14 suggest that the DYT prefix may be more appropriate, highlighting the need to reconsider their nomenclature, and the importance of systematic reviews. Keywords: dystonia; parkinsonism; GLB1; SLC6A3; SLC30A10; SLC39A14; PLA2G6; MDSGene Author: Jon Rodriguez-Antiguedad, Rajasumi Rajalingam, Clara Krüger, Daniel Teixeira-dos-Santos, Christine Sun, Elias Fernandez-Toledo, Alexia Duarte, Paula Saffie-Awad, Matthew J. Barrett, Joseph L. Flanigan, Maziar Emamikhah, Neepa Patel, Marta San Luciano, Christine Cooper, Natascha Bahr, Odinachi Oguh, Alissa Buhrmann, Merle Vater, Rabea Fuchshofen, Franca Vulinovic, Maik-Iven Parreidt, Anne Weissbach, Katja Lohmann, Christine Klein, Connie Marras and Sarah Camargos Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Apr 25 12:43:42 2025 CEST ModDate: Fri Apr 25 12:47:59 2025 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3364459 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- QKZKVH+VnURWPalladioL Type 1 Custom yes yes yes 10 0 TRETAO+URWPalladioL-Roma Type 1 Custom yes yes yes 16 0 LCSIDH+URWPalladioL-Bold Type 1 Custom yes yes yes 22 0 HTGPZO+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 IVCWOQ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 32 0 WVWPDJ+PazoMath-Italic Type 1 Builtin yes yes yes 64 0 KCJJCN+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 75 0 KCJJDN+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 81 0 KCJJEO+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 87 0 KCJJEP+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 93 0 KCJJFA+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 96 0 KCJJFB+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 99 0 KCJJNA+PalatinoLinotype-BoldItalic TrueType WinAnsi yes yes no 102 0 KCJJOB+PalatinoLinotype-Roman TrueType MacRoman yes yes no 105 0 AAAAAC+Aptos-Italic TrueType WinAnsi yes yes yes 148 0 LWLIVD+EURM10 Type 1 Builtin yes yes yes 172 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-03-28 04:12:10 CET RepresentationInformation: 322607.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-03-27 11:31:26 CET Size: 3364459 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 323 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: MDSGene Destination: subsection.2.1 Item: Title: Literature Search Destination: subsection.2.2 Item: Title: Inclusion and Exclusion Criteria for Patients and Genetic Variants Destination: subsection.2.3 Item: Title: Data Collection Process Destination: subsection.2.4 Item: Title: Pathogenicity Scoring Destination: subsection.2.5 Item: Title: Statistical Analyses Destination: subsection.2.6 Item: Title: Results Destination: section.3 Children: Item: Title: GLB1 Destination: subsection.3.1 Item: Title: SLC6A3 Destination: subsection.3.2 Item: Title: SLC30A10 Destination: subsection.3.3 Item: Title: SLC39A14 Destination: subsection.3.4 Item: Title: PLA2G6 Destination: subsection.3.5 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Genotype Phenotype Relations for the Dystonia-Parkinsonism Genes GLB1, SLC6A3, SLC30A10, SLC39A14, and PLA2G6: MDSGene Systematic Review Author: Jon Rodriguez-Antiguedad, Rajasumi Rajalingam, Clara Krüger, Daniel Teixeira-dos-Santos, Christine Sun, Elias Fernandez-Toledo, Alexia Duarte, Paula Saffie-Awad, Matthew J. Barrett, Joseph L. Flanigan, Maziar Emamikhah, Neepa Patel, Marta San Luciano, Christine Cooper, Natascha Bahr, Odinachi Oguh, Alissa Buhrmann, Merle Vater, Rabea Fuchshofen, Franca Vulinovic, Maik-Iven Parreidt, Anne Weissbach, Katja Lohmann, Christine Klein, Connie Marras and Sarah Camargos Subject: The Movement Disorders Society recommends the DYT/PARK prefix for genes where dystonia and parkinsonism are prominent in approximately half or more of patients. This systematic review explores the genotype phenotype correlations of GLB1, SLC6A3, SLC30A10, PLA2G6, and SLC39A14 recently classified as DYT SLC39A14 and historically linked to dystonia-parkinsonism. We searched PubMed and the Human Gene Mutation Database using standardized terms, including English-language, peer-reviewed publications up to February 2024. Following the MDSGene protocol, we extracted individual-level data on patients with biallelic pathogenic variants and at least one movement disorder. Features were marked “missing” if not explicitly reported. Of 1828 articles, 128 were eligible. We identified 386 patients and 262 variants. The median age at onset was 3 years for GLB1, 3 months for SLC6A3, 2.5 years for SLC30A10, 1.5 years for SLC39A14, and 16 years for PLA2G6. Missing data may reflect underreporting of negative findings. Case reports/serie, may bias toward atypical presentations. Our analysis showed dystonia-parkinsonism predominates in SLC6A3 and PLA2G6, while GLB1, SLC30A10, and SLC39A1 show predominantly dystonic phenotypes with a low frequency of parkinsonism. Ataxia was common in GLB1 and PLA2G6. Awareness of these phenotypes is essential for early diagnosis and intervention, particularly in treatable conditions like SLC30A10 or SLC39A14. The predominantly dystonic phenotype in GLB1, SLC30A10, and SLC39A14 suggest that the DYT prefix may be more appropriate, highlighting the need to reconsider their nomenclature, and the importance of systematic reviews. Keywords: dystonia; parkinsonism; GLB1; SLC6A3; SLC30A10; SLC39A14; PLA2G6; MDSGene Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Apr 25 12:43:42 CEST 2025 ModDate: Fri Apr 25 12:47:59 CEST 2025 ID: 0x0da0a5d397f091836947350b378156df, 0x0da0a5d397f091836947350b378156df Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: IVCWOQ+URWPalladioL-BoldItal FontSubset: true FirstChar: 48 LastChar: 83 FontDescriptor: FontName: IVCWOQ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: TRETAO+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: TRETAO+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: WVWPDJ+PazoMath-Italic FontSubset: true FirstChar: 99 LastChar: 99 FontDescriptor: FontName: WVWPDJ+PazoMath-Italic Flags: 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