title: A novel homozygous DJ1 mutation causes parkinsonism and ALS in a Turkish family.
abstract: DJ1 mutations (PARK7) are among the monogenic causes of early-onset autosomal recessive parkinsonism. Here, we report clinical and genetic findings in a family with Turkish origin carrying a new DJ1 mutation and presenting with early-onset levodopa responsive parkinsonism and signs of amyotrophic lateral sclerosis (ALS).
  
  
  
  The family consisted of 12 members including 10 offsprings of whom three were affected. All family members underwent detailed clinical examination. DNA samples from the index case, his unaffected sister, and his parents were subjected to whole genome sequencing analysis.
  
  
  
  The index case 38-year-old man developed left hand tremor at the age of 24 years. He had progressive asymmetrical parkinsonism, depression and developed signs of ALS within 4 years. His two affected sisters had young-onset asymmetrical tremor-dominant parkinsonism with signs of ALS. A new homozygous p.Q45X mutation in exon 3 in DJ1 was found in all three patients. Their unaffected parents and one clinically healthy sibling were found to be heterozygous for this mutation.
  
  
  
  This is the second report of DJ1 mutations associated with parkinsonism and ALS. This is relevant for genetic counseling as well as for understanding the pathogenesis of the broad spectrum of parkinsonism-ALS disease complex.
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Capa, 34390 Istanbul, Turkey. Electronic address: hasmet@yahoo.com.
authors.forename: Hasmet A
authors.initials: HA
authors.lastname: Hanagasi
authors.affiliation: Dept. of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Anamika
authors.initials: A
authors.lastname: Giri
authors.affiliation: Department Molecular Biology and Genetics, Neurodegeneration Research Laboratory, Bogazici University, 34342, Istanbul, Turkey.
authors.forename: Ece
authors.initials: E
authors.lastname: Kartal
authors.affiliation: Institute for Experimental Medicine, Genetics Department, Istanbul University, Istanbul, Turkey.
authors.forename: Gamze
authors.initials: G
authors.lastname: Guven
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Capa, 34390 Istanbul, Turkey.
authors.forename: Başar
authors.initials: B
authors.lastname: Bilgiç
authors.affiliation: Dept. of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Hauser
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Capa, 34390 Istanbul, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Emre
authors.affiliation: Dept. of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
authors.affiliation: Department Molecular Biology and Genetics, Neurodegeneration Research Laboratory, Bogazici University, 34342, Istanbul, Turkey.
authors.forename: Nazlı
authors.initials: N
authors.lastname: Basak
authors.affiliation: Dept. of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.affiliation: Dept. of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Javier
authors.initials: J
authors.lastname: Simón-Sánchez
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Capa, 34390 Istanbul, Turkey; Dept. of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Ebba
authors.initials: E
authors.lastname: Lohmann
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000235:genetics*; D019295:Computational Biology; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics*; D000071617:Protein Deglycase DJ-1 / Q000235:genetics*; D012720:Severity of Illness Index; D014421:Turkey
chemical_list: C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1
keywords: Amyotrophic lateral sclerosis; DJ1; PARK7; Parkinson's disease