Hamidreza Khodadadi1, Luis J Azcona2,3, Vajiheh Aghamollaii4, Mir Davood Omrani1, Masoud Garshasbi5, Shaghayegh Taghavi1, Abbas Tafakhori6, Gholam Ali Shahidi7, Javad Jamshidi8, Hossein Darvish1, Coro Paisán-Ruiz3,9,10,11,12. 1. Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Department of Neurosciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 3. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 4. Department of Neurology, Roozbeh Psychiatry Hospital, Tehran University of Medical Sciences, Tehran, Iran. 5. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 6. Department of Neurology, School of Medicine, Imam Khomeini Hospital and Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran. 7. Movement Disorders Clinic, Hazrat Rassol Hospital, Iran University of Medical Sciences, Tehran, Iran. 8. Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran. 9. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York, USA. 10. Department of Genetics and Genomic sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York, USA. 11. Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York, USA. 12. Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Abstract
INTRODUCTION: Atypical parkinsonism is a neurodegenerative disease that includes diverse neurological and psychiatric manifestations. OBJECTIVES: We aimed to identify the disease-cauisng mutations in a consanguineous family featuring intellectual disability and parkinsonism. METHODS: Full phenotypic characterization, followed by genome-wide single-nucleotide polymorphism genotyping and whole-genome sequencing, was carried out in all available family members. RESULTS: The chromosome, 2p23.3, was identified as the disease-associated locus, and a homozygous PTRHD1 mutation (c.157C>T) was then established as the disease-causing mutation. The pathogenicity of this PTRHD1 mutation was supported by its segregation with the disease status, its location in a functional domain of the encoding protein, as well as its absence in public databases and ethnicity-matched control chromosomes. CONCLUSION: Given the role of 2p23 locus in patients with intellectual disability and the previously reported PTRHD1 mutation (c.155G>A) in patients with parkinsonism and cognitive dysfunction, we concluded that the PTRHD1 mutation identified in this study is likely to be responsible for the phenotypic features of the family under consideration.
INTRODUCTION:Atypical parkinsonism is a neurodegenerative disease that includes diverse neurological and psychiatric manifestations. OBJECTIVES: We aimed to identify the disease-cauisng mutations in a consanguineous family featuring intellectual disability and parkinsonism. METHODS: Full phenotypic characterization, followed by genome-wide single-nucleotide polymorphism genotyping and whole-genome sequencing, was carried out in all available family members. RESULTS: The chromosome, 2p23.3, was identified as the disease-associated locus, and a homozygous PTRHD1 mutation (c.157C>T) was then established as the disease-causing mutation. The pathogenicity of this PTRHD1 mutation was supported by its segregation with the disease status, its location in a functional domain of the encoding protein, as well as its absence in public databases and ethnicity-matched control chromosomes. CONCLUSION: Given the role of 2p23 locus in patients with intellectual disability and the previously reported PTRHD1 mutation (c.155G>A) in patients with parkinsonism and cognitive dysfunction, we concluded that the PTRHD1 mutation identified in this study is likely to be responsible for the phenotypic features of the family under consideration.
Authors: Catharine E Krebs; Siamak Karkheiran; James C Powell; Mian Cao; Vladimir Makarov; Hossein Darvish; Gilbert Di Paolo; Ruth H Walker; Gholam Ali Shahidi; Joseph D Buxbaum; Pietro De Camilli; Zhenyu Yue; Coro Paisán-Ruiz Journal: Hum Mutat Date: 2013-07-19 Impact factor: 4.878
Authors: Suzanne Lesage; Valérie Drouet; Elisa Majounie; Vincent Deramecourt; Maxime Jacoupy; Aude Nicolas; Florence Cormier-Dequaire; Sidi Mohamed Hassoun; Claire Pujol; Sorana Ciura; Zoi Erpapazoglou; Tatiana Usenko; Claude-Alain Maurage; Mourad Sahbatou; Stefan Liebau; Jinhui Ding; Basar Bilgic; Murat Emre; Nihan Erginel-Unaltuna; Gamze Guven; François Tison; Christine Tranchant; Marie Vidailhet; Jean-Christophe Corvol; Paul Krack; Anne-Louise Leutenegger; Michael A Nalls; Dena G Hernandez; Peter Heutink; J Raphael Gibbs; John Hardy; Nicholas W Wood; Thomas Gasser; Alexandra Durr; Jean-François Deleuze; Meriem Tazir; Alain Destée; Ebba Lohmann; Edor Kabashi; Andrew Singleton; Olga Corti; Alexis Brice Journal: Am J Hum Genet Date: 2016-03-03 Impact factor: 11.025
Authors: Timothy J Jarome; Janine L Kwapis; Jada J Hallengren; Scott M Wilson; Fred J Helmstetter Journal: Learn Mem Date: 2013-12-16 Impact factor: 2.460
Authors: Marina V Shulskaya; Anelya Kh Alieva; Ivan N Vlasov; Vladimir V Zyrin; Ekaterina Yu Fedotova; Natalia Yu Abramycheva; Tatiana S Usenko; Andrei F Yakimovsky; Anton K Emelyanov; Sofya N Pchelina; Sergei N Illarioshkin; Petr A Slominsky; Maria I Shadrina Journal: Front Aging Neurosci Date: 2018-05-15 Impact factor: 5.750