Ebba Lohmann1,2, Anne-Sophie Coquel3, Aurélie Honoré3, Hakan Gurvit1, Hasmet Hanagasi1, Murat Emre1, Anne L Leutenegger4, Valérie Drouet3, Mourad Sahbatou5, Gamze Guven6, Nihan Erginel-Unaltuna6, Jean-Francois Deleuze7, Suzanne Lesage3, Alexis Brice3,8. 1. Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 2. Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany. 3. Sorbonne Université, UPMC Univ Paris 06, UM 1127, ICM, Paris, France; Inserm, U 1127, ICM, Paris, France; Cnrs, UMR 7225, ICM, Paris, France; ICM, Paris, F-75013, Paris, France. 4. Inserm, U946, Paris, France; Université Paris Diderot, Institut Universitaire d'Hématologie, Paris, France. 5. Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France. 6. Institute for Experimental Medicine, Genetics Department, Istanbul University, Istanbul, Turkey. 7. Commissariat à l'Energie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France. 8. AP-HP, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, F-75013, Paris, France.
Abstract
BACKGROUND: Recessive mutations in the F-box protein 7 gene (FBXO7; PARK15) have been identified as a cause of the parkinsonian-pyramidal syndrome. Here, we report clinical and genetic findings in a Turkish family with novel FBXO7 mutations. METHODS: Whole exome and targeted Sanger sequencing were performed for genetic analysis in a family with two members affected by Parkinson's disease (PD). All family members underwent detailed clinical, mental, and neurological examination. RESULTS: The new p.L34R (c.101 T>G) FBXO7 mutation was detected in a homozygous state in two Turkish sibs with typical levodopa-responsive PD. CONCLUSION: This is the first time a FBXO7 mutation has been identified that causes a phenotype compatible with typical idiopathic PD and presents with some of its common nonmotor features, such as rapid eye movement sleep behavior disorder, depression, and anxiety.
BACKGROUND: Recessive mutations in the F-box protein 7 gene (FBXO7; PARK15) have been identified as a cause of the parkinsonian-pyramidal syndrome. Here, we report clinical and genetic findings in a Turkish family with novel FBXO7 mutations. METHODS: Whole exome and targeted Sanger sequencing were performed for genetic analysis in a family with two members affected by Parkinson's disease (PD). All family members underwent detailed clinical, mental, and neurological examination. RESULTS: The new p.L34R (c.101 T>G) FBXO7 mutation was detected in a homozygous state in two Turkish sibs with typical levodopa-responsive PD. CONCLUSION: This is the first time a FBXO7 mutation has been identified that causes a phenotype compatible with typical idiopathic PD and presents with some of its common nonmotor features, such as rapid eye movement sleep behavior disorder, depression, and anxiety.
Authors: Felipe Roberti Teixeira; Suzanne J Randle; Shachi P Patel; Tycho E T Mevissen; Grasilda Zenkeviciute; Tie Koide; David Komander; Heike Laman Journal: Biochem J Date: 2016-08-08 Impact factor: 3.857