Case Report: Novel ATP13A2 pathogenic variants associated with early-onset parkinsonism and a mini-review
ATP13A2 is a gene localized on chromosome 1p36.13 and coding for a transmembrane protein found in the lysosomes and late endosomes, which is involved in many cellular metabolic activities. Pathogenetic variants of ATP13A2 are associated with a wide range of neurodegenerative disorder including Kufor...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1588812/full |
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| author | Leonardo Affronte Leonardo Affronte Antonella Pini Claudia Pizzoli Emanuele Coccia Serena Mazzone Arber Golemi Melania Giannotta Duccio Maria Cordelli Duccio Maria Cordelli Valerio Carelli Valerio Carelli Alessandro Vaisfeld Alessandro Vaisfeld Flavia Palombo |
| author_facet | Leonardo Affronte Leonardo Affronte Antonella Pini Claudia Pizzoli Emanuele Coccia Serena Mazzone Arber Golemi Melania Giannotta Duccio Maria Cordelli Duccio Maria Cordelli Valerio Carelli Valerio Carelli Alessandro Vaisfeld Alessandro Vaisfeld Flavia Palombo |
| author_sort | Leonardo Affronte |
| collection | DOAJ |
| description | ATP13A2 is a gene localized on chromosome 1p36.13 and coding for a transmembrane protein found in the lysosomes and late endosomes, which is involved in many cellular metabolic activities. Pathogenetic variants of ATP13A2 are associated with a wide range of neurodegenerative disorder including Kufor Rakeb syndrome (KRS), a rare autosomal recessive form of levodopa responsive juvenile onset parkinsonism (MxMD-ATP13A2), characterized by rapidly progressive muscular stiffness, bradykinesia, spasticity, pyramidal findings, dementia and supranuclear gaze palsy. The aim of this study is to provide detailed clinical descriptions of two siblings, carriers of novel biallelic ATP13A2 variants. One of them showed KRS levodopa-responsive motor dystonic features at the age of 10 years preceded by moderate cognitive impairment, while the other only showed mild cognitive impairment at our last evaluation at 11 years of age. Additionally, we reviewed the previously published cases, focusing on early signs and symptoms, clinical evolution and response to therapy. To our knowledge, this is the only work that groups all reported KRS patients and compares their clinical and molecular features. |
| format | Article |
| id | doaj-art-5dc6a3f85d644db8a893cebb0b1b7a34 |
| institution | DOAJ |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj-art-5dc6a3f85d644db8a893cebb0b1b7a342025-08-20T03:09:24ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-07-011610.3389/fgene.2025.15888121588812Case Report: Novel ATP13A2 pathogenic variants associated with early-onset parkinsonism and a mini-reviewLeonardo Affronte0Leonardo Affronte1Antonella Pini2Claudia Pizzoli3Emanuele Coccia4Serena Mazzone5Arber Golemi6Melania Giannotta7Duccio Maria Cordelli8Duccio Maria Cordelli9Valerio Carelli10Valerio Carelli11Alessandro Vaisfeld12Alessandro Vaisfeld13Flavia Palombo14Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, ItalyIRCCS Istituto delle Scienze Neurologiche di Bologna, Pediatric Neuromuscular Unit, UO Neuropsichiatria dell’Età Pediatrica, Bologna, ItalyIRCCS Istituto delle Scienze Neurologiche di Bologna, Pediatric Neuromuscular Unit, UO Neuropsichiatria dell’Età Pediatrica, Bologna, ItalyIRCCS Istituto Delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria dell'Età Pediatrica, Bologna, ItalyMedical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyIRCCS Istituto Delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria dell'Età Pediatrica, Bologna, ItalyMedicina Nucleare, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyIRCCS Istituto delle Scienze Neurologiche di Bologna, Pediatric Neuromuscular Unit, UO Neuropsichiatria dell’Età Pediatrica, Bologna, ItalyIRCCS Istituto Delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria dell'Età Pediatrica, Bologna, ItalyDepartment of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, ItalyDepartment of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, ItalyIRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, ItalyMedical Genetics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyIRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, ItalyATP13A2 is a gene localized on chromosome 1p36.13 and coding for a transmembrane protein found in the lysosomes and late endosomes, which is involved in many cellular metabolic activities. Pathogenetic variants of ATP13A2 are associated with a wide range of neurodegenerative disorder including Kufor Rakeb syndrome (KRS), a rare autosomal recessive form of levodopa responsive juvenile onset parkinsonism (MxMD-ATP13A2), characterized by rapidly progressive muscular stiffness, bradykinesia, spasticity, pyramidal findings, dementia and supranuclear gaze palsy. The aim of this study is to provide detailed clinical descriptions of two siblings, carriers of novel biallelic ATP13A2 variants. One of them showed KRS levodopa-responsive motor dystonic features at the age of 10 years preceded by moderate cognitive impairment, while the other only showed mild cognitive impairment at our last evaluation at 11 years of age. Additionally, we reviewed the previously published cases, focusing on early signs and symptoms, clinical evolution and response to therapy. To our knowledge, this is the only work that groups all reported KRS patients and compares their clinical and molecular features.https://www.frontiersin.org/articles/10.3389/fgene.2025.1588812/fullATP13A2WESjuvenile onset parkinsonismkufor rakeb syndromeKRS cases revision |
| spellingShingle | Leonardo Affronte Leonardo Affronte Antonella Pini Claudia Pizzoli Emanuele Coccia Serena Mazzone Arber Golemi Melania Giannotta Duccio Maria Cordelli Duccio Maria Cordelli Valerio Carelli Valerio Carelli Alessandro Vaisfeld Alessandro Vaisfeld Flavia Palombo Case Report: Novel ATP13A2 pathogenic variants associated with early-onset parkinsonism and a mini-review Frontiers in Genetics ATP13A2 WES juvenile onset parkinsonism kufor rakeb syndrome KRS cases revision |
| title | Case Report: Novel ATP13A2 pathogenic variants associated with early-onset parkinsonism and a mini-review |
| title_full | Case Report: Novel ATP13A2 pathogenic variants associated with early-onset parkinsonism and a mini-review |
| title_fullStr | Case Report: Novel ATP13A2 pathogenic variants associated with early-onset parkinsonism and a mini-review |
| title_full_unstemmed | Case Report: Novel ATP13A2 pathogenic variants associated with early-onset parkinsonism and a mini-review |
| title_short | Case Report: Novel ATP13A2 pathogenic variants associated with early-onset parkinsonism and a mini-review |
| title_sort | case report novel atp13a2 pathogenic variants associated with early onset parkinsonism and a mini review |
| topic | ATP13A2 WES juvenile onset parkinsonism kufor rakeb syndrome KRS cases revision |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1588812/full |
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