title: The distinct genetic pattern of ALS in Turkey and novel mutations.
abstract: The frequency of amyotrophic lateral sclerosis (ALS) mutations has been extensively investigated in several populations; however, a systematic analysis in Turkish cases has not been reported so far. In this study, we screened 477 ALS patients for mutations, including 116 familial ALS patients from 82 families and 361 sporadic ALS (sALS) cases. Patients were genotyped for C9orf72 (18.3%), SOD1 (12.2%), FUS (5%), TARDBP (3.7%), and UBQLN2 (2.4%) gene mutations, which together account for approximately 40% of familial ALS in Turkey. No SOD1 mutations were detected in sALS patients; however, C9orf72 (3.1%) and UBQLN2 (0.6%) explained 3.7% of sALS in the population. Exome sequencing revealed mutations in OPTN, SPG11, DJ1, PLEKHG5, SYNE1, TRPM7, and SQSTM1 genes, many of them novel. The spectrum of mutations reflect both the distinct genetic background and the heterogeneous nature of the Turkish ALS population.
authors: Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Molecular Biology and Genetics Department, Boğaziçi University, Istanbul, Turkey.
authors: Aslıhan
authors: A
authors: Özoğuz
authors: Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Molecular Biology and Genetics Department, Boğaziçi University, Istanbul, Turkey.
authors: Özgün
authors: Ö
authors: Uyan
authors: Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Molecular Biology and Genetics Department, Boğaziçi University, Istanbul, Turkey.
authors: Güneş
authors: G
authors: Birdal
authors: Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Molecular Biology and Genetics Department, Boğaziçi University, Istanbul, Turkey.
authors: Ceren
authors: C
authors: Iskender
authors: Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Molecular Biology and Genetics Department, Boğaziçi University, Istanbul, Turkey.
authors: Ece
authors: E
authors: Kartal
authors: Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Molecular Biology and Genetics Department, Boğaziçi University, Istanbul, Turkey.
authors: Suna
authors: S
authors: Lahut
authors: Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Molecular Biology and Genetics Department, Boğaziçi University, Istanbul, Turkey.
authors: Özgür
authors: Ö
authors: Ömür
authors: Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Molecular Biology and Genetics Department, Boğaziçi University, Istanbul, Turkey.
authors: Zeynep Sena
authors: ZS
authors: Agim
authors: Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Molecular Biology and Genetics Department, Boğaziçi University, Istanbul, Turkey.
authors: Aslı Gündoğdu
authors: AG
authors: Eken
authors: Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Molecular Biology and Genetics Department, Boğaziçi University, Istanbul, Turkey.
authors: Nesli Ece
authors: NE
authors: Sen
authors: Computer Engineering Department, Boğaziçi University, Istanbul, Turkey.
authors: Pınar
authors: P
authors: Kavak
authors: Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Molecular Biology and Genetics Department, Boğaziçi University, Istanbul, Turkey.
authors: Ceren
authors: C
authors: Saygı
authors: Neurology Department, Medical School, University of Massachusetts, Worcester, MA, USA.
authors: Peter C
authors: PC
authors: Sapp
authors: Neurology Department, Medical School, University of Massachusetts, Worcester, MA, USA.
authors: Pamela
authors: P
authors: Keagle
authors: Neurology Department, Istanbul Medical School, Istanbul University, Istanbul, Turkey.
authors: Yeşim
authors: Y
authors: Parman
authors: Neurology Department, Medical School, Hacettepe University, Ankara, Turkey.
authors: Ersin
authors: E
authors: Tan
authors: Neurology Department, Medical School, Çukurova University, Adana, Turkey.
authors: Filiz
authors: F
authors: Koç
authors: Neurology Department, Istanbul Medical School, Istanbul University, Istanbul, Turkey.
authors: Feza
authors: F
authors: Deymeer
authors: Neurology Department, Istanbul Medical School, Istanbul University, Istanbul, Turkey.
authors: Piraye
authors: P
authors: Oflazer
authors: Neurology Department, Istanbul Medical School, Istanbul University, Istanbul, Turkey.
authors: Haşmet
authors: H
authors: Hanağası
authors: Neurology Department, Istanbul Medical School, Istanbul University, Istanbul, Turkey.
authors: Hakan
authors: H
authors: Gürvit
authors: Neurology Department, Istanbul Medical School, Istanbul University, Istanbul, Turkey.
authors: Başar
authors: B
authors: Bilgiç
authors: Neurology Department, Istanbul Medical School, Istanbul University, Istanbul, Turkey.
authors: Hacer
authors: H
authors: Durmuş
authors: Department of Neurology, Liv Hospital, Istanbul, Turkey.
authors: Mustafa
authors: M
authors: Ertaş
authors: Faculty of Medicine, Department of Neurology, Sakarya University, Sakarya, Turkey.
authors: Dilcan
authors: D
authors: Kotan
authors: Neurology Department, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
authors: Mehmet Ali
authors: MA
authors: Akalın
authors: Department of Neurology, Medical Park Izmir Hospital, Izmir, Turkey.
authors: Halil
authors: H
authors: Güllüoğlu
authors: Department of Neurology, School of Medicine, Uludağ University, Bursa, Turkey.
authors: Mehmet
authors: M
authors: Zarifoğlu
authors: Bakırköy Research and Training Hospital for Neurologic and Psychiatric Diseases, Istanbul, Turkey.
authors: Fikret
authors: F
authors: Aysal
authors: Department of Microbiology, Haydarpaşa Numune Education and Research Hospital, Istanbul, Turkey.
authors: Nilgün
authors: N
authors: Döşoğlu
authors: Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
authors: Kaya
authors: K
authors: Bilguvar
authors: Department of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
authors: Murat
authors: M
authors: Günel
authors: Chemical and Biological Engineering Department, Koç University, Istanbul, Turkey.
authors: Özlem
authors: Ö
authors: Keskin
authors: Department of Anesthesiology and Reanimation, American Hospital, Istanbul, Turkey.
authors: Tahsin
authors: T
authors: Akgün
authors: Department of Pathology and Laboratory Medicine, Samuel Lunenfeld Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors: Hilmi
authors: H
authors: Özçelik
authors: Neurology Department, Medical School, University of Massachusetts, Worcester, MA, USA.
authors: John E
authors: JE
authors: Landers
authors: Neurology Department, Medical School, University of Massachusetts, Worcester, MA, USA.
authors: Robert H
authors: RH
authors: Brown
authors: Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory (NDAL), Molecular Biology and Genetics Department, Boğaziçi University, Istanbul, Turkey. Electronic address: basak@boun.edu.tr.
authors: A Nazlı
authors: AN
authors: Başak
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D000073885:C9orf72 Protein; D018797:Cell Cycle Proteins / Q000235:genetics; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000235:genetics; D059472:Exome / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D000071617:Protein Deglycase DJ-1; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D000071456:Sequestosome-1 Protein; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D050053:TRPM Cation Channels / Q000235:genetics; D035582:Transcription Factor TFIIIA / Q000235:genetics; D014421:Turkey; D014452:Ubiquitins / Q000235:genetics; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C000599550:FUS protein, human; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C409460:OPTN protein, human; D015513:Oncogene Proteins; C522397:PLEKHG5 protein, human; D011506:Proteins; D034702:RNA-Binding Protein FUS; C000606290:SOD1 protein, human; C520412:SPG11 protein, human; C099718:SQSTM1 protein, human; C415465:SYNE1 protein, human; D000071456:Sequestosome-1 Protein; C000598624:TARDBP protein, human; D050053:TRPM Cation Channels; D035582:Transcription Factor TFIIIA; C405662:UBQLN2 protein, human; D014452:Ubiquitins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1
keywords: ALS; C9orf72; FUS; SOD1; TDP-43; Turkey