title: PLA2G6 mutations associated with a continuous clinical spectrum from neuroaxonal dystrophy to hereditary spastic paraplegia.
abstract: PLA2G6-associated neurodegeneration (PLAN) and hereditary spastic paraplegia (HSP) are 2 groups of heterogeneous neurodegenerative diseases. In this study, we report PLA2G6 gene mutations in 3 families from Turkey, Morocco, and Romania. Two affected Turkish siblings presenting HSP adds the disease to PLAN phenotypes. They were homozygous for the PLA2G6 missense c.2239C>T, p.Arg747Trp variant and the ages of onset were 9 and 21. Parkinsonism, dystonia or cognitive decline were not the clinical elements in these patients contrary to the cases that has been previously reported with the same variant, however, iron accumulation was evident in their cranial magnetic resonance imaging. The Moroccan patient was homozygous for a novel missense c.1786C>T, p.Leu596Phe variant and the Romanian patient had 2 novel mutations; c.1898C>T, p.Ala633Val and c.1765_1768del, p.Ser589ThrfsTer76. Both of these patients conformed better to childhood onset PLAN with the age of onset at 4 and 7 years, respectively. Interestingly, all identified mutations were affecting the highly conserved patatin-like phospholipase domain of the PLA2G6 protein.
authors.affiliation: Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Ozes
authors.affiliation: Department of Neurology, Bakirkoy Training and Research Hospital for Psychiatry and Neurological Diseases, Istanbul, Turkey.
authors.forename: N
authors.initials: N
authors.lastname: Karagoz
authors.affiliation: Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and Centre of Neurology, Tuebingen, Germany.|University of Tuebingen, German Research Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schüle
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: A
authors.initials: A
authors.lastname: Rebelo
authors.affiliation: Neurogenetics Group, FPGMX-IDIS, Santiago de Compostela, Spain.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Sobrido
authors.affiliation: Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Harmuth
authors.affiliation: Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and Centre of Neurology, Tuebingen, Germany.|University of Tuebingen, German Research Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Synofzik
authors.affiliation: Servicio de Neurologia Pediátrica, Hospital Universitario La Paz, Prof. Asociado Departamento de Pediatria, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: S I P
authors.initials: SIP
authors.lastname: Pascual
authors.affiliation: Department of Neurology, Bakirkoy Training and Research Hospital for Psychiatry and Neurological Diseases, Istanbul, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Colak
authors.affiliation: Department of Neurology, Bakirkoy Training and Research Hospital for Psychiatry and Neurological Diseases, Istanbul, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Ciftci-Kavaklioglu
authors.affiliation: Department of Radiology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Kara
authors.affiliation: Neurogenetics Group, FPGMX-IDIS, Santiago de Compostela, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ordóñez-Ugalde
authors.affiliation: Neurogenetics Group, FPGMX-IDIS, Santiago de Compostela, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Quintáns
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: M A
authors.initials: MA
authors.lastname: Gonzalez
authors.affiliation: Department of Neurology, Bakirkoy Training and Research Hospital for Psychiatry and Neurological Diseases, Istanbul, Turkey.
authors.forename: A
authors.initials: A
authors.lastname: Soysal
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: S
authors.initials: S
authors.lastname: Zuchner
authors.affiliation: Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey.
authors.forename: E
authors.identifier: http://orcid.org/0000-0003-3131-6123
authors.initials: E
authors.lastname: Battaloglu
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D019150:Neuroaxonal Dystrophies / Q000235:genetics*; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D055815:Young Adult
chemical_list: D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human
keywords: 
  PLA2G6-associated neurodegeneration, PLAN; HSP, next-generation sequencing; hereditary spastic paraplegia