title: SORT1 Mutation Resulting in Sortilin Deficiency and p75(NTR) Upregulation in a Family With Essential Tremor.
abstract: *These authors contributed equally to this work.Essential tremor (ET) is the most prevalent movement disorder affecting millions of people in the United States. Although a positive family history is one of the most important risk factors for ET, the genetic causes of ET remain unknown. In this study, whole exome sequencing and subsequent approaches were performed in a family with an autosomal dominant form of early-onset ET. Functional analyses including mutagenesis, cell culture, gene expression, enzyme-linked immunosorbent, and apoptosis assays were also performed. A disease-segregating mutation (p.Gly171Ala), absent in normal population, was identified in the SORT1 gene. The p.Gly171Ala mutation was shown not only to impair the expression of its encoding protein sortilin but also the mRNA levels of its binding partner p75 neurotrophin receptor that is known to be implicated in brain injury, neuronal apoptosis, and neurotransmission.
authors: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Elena
authors: E
authors: Sánchez
authors: Biodonostia Research Institute, University of the Basque Country, San Sebastián, Gipuzkoa, Spain Department of Neurology, Hospital Universitario Donostia, San Sebastián, Guipuzcoa, Spain Centro de investigación biomédica en Red para enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors: Alberto
authors: A
authors: Bergareche
authors: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Catharine E
authors: CE
authors: Krebs
authors: Biodonostia Research Institute, University of the Basque Country, San Sebastián, Gipuzkoa, Spain Department of Neurology, Hospital Universitario Donostia, San Sebastián, Guipuzcoa, Spain Centro de investigación biomédica en Red para enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors: Ana
authors: A
authors: Gorostidi
authors: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Vladimir
authors: V
authors: Makarov
authors: Biodonostia Research Institute, University of the Basque Country, San Sebastián, Gipuzkoa, Spain Department of Neurology, Hospital Universitario Donostia, San Sebastián, Guipuzcoa, Spain Centro de investigación biomédica en Red para enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors: Javier
authors: J
authors: Ruiz-Martinez
authors: Department of Medicine, The Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Alejo
authors: A
authors: Chorny
authors: Biodonostia Research Institute, University of the Basque Country, San Sebastián, Gipuzkoa, Spain Department of Neurology, Hospital Universitario Donostia, San Sebastián, Guipuzcoa, Spain Centro de investigación biomédica en Red para enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain Department of Neurosciences, University of the Basque Country, San Sebastián, Guipuzcoa, Spain.
authors: Adolfo
authors: A
authors: Lopez de Munain
authors: Biodonostia Research Institute, University of the Basque Country, San Sebastián, Gipuzkoa, Spain Department of Neurology, Hospital Universitario Donostia, San Sebastián, Guipuzcoa, Spain Centro de investigación biomédica en Red para enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain Department of Neurosciences, University of the Basque Country, San Sebastián, Guipuzcoa, Spain.
authors: Jose Felix
authors: JF
authors: Marti-Masso
authors: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA Departments of Psychiatry and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA Friedman Brain and Mindich Child Health and Development Institutes, Icahn School of Medicine at Mount Sinai, New York, NY, USA coro.paisan-ruiz@mssm.edu.
authors: Coro
authors: C
authors: Paisán-Ruiz
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D020329:Essential Tremor / Q000235:genetics* / Q000503:physiopathology; D005192:Family Health; D005260:Female; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D011795:Surveys and Questionnaires; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics*; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D000099183:Sortilin; C484065:NGFR protein, human
keywords: SORT1 mutation; p75NTR upregulation; sortilin downregulation; tremor