A comprehensive, multidisciplinary, precision medicine approach to discover effective therapy for an undiagnosed, progressive, fibroinflammatory disease.
Identifieur interne : 000229 ( Main/Exploration ); précédent : 000228; suivant : 000230A comprehensive, multidisciplinary, precision medicine approach to discover effective therapy for an undiagnosed, progressive, fibroinflammatory disease.
Auteurs : Bernadette R. Gochuico [États-Unis] ; Shira G. Ziegler [États-Unis] ; Nicholas S. Ten [États-Unis] ; Nicholas J. Balanda [États-Unis] ; Christopher E. Mason [États-Unis] ; Paul Zumbo [États-Unis] ; Colleen A. Evans [États-Unis] ; Carter Van Waes [États-Unis] ; William A. Gahl [États-Unis] ; May C V. Malicdan [États-Unis]Source :
- Translational research : the journal of laboratory and clinical medicine [ 1878-1810 ] ; 2020.
Abstract
Precision medicine has generated diagnoses for many patients with challenging undiagnosed disorders. Some individuals remain without a diagnosis despite comprehensive testing, and this impedes their treatment. This report addresses the role of personalized medicine in identifying effective therapy for an undiagnosed disease. A 22-year-old woman presented with chronic severe recurrent trismus, facial pain, progressive multicentric inflammatory and fibrotic masses, and high C-reactive protein. Sites of disease included the pterygomaxillary region, masseter muscles, mandible, lung, pericardium, intrabdominal cavity, and retroperitoneum. A diagnosis was not established after an extensive assessment, including multiple biopsies. The patient was subsequently evaluated under the Undiagnosed Diseases Program at the National Institutes of Health. Large scale genotyping, proteomic studies, and in vitro and gene expression analyses of fibroblasts obtained from a major disease locus were performed. Germline genetic testing did not identify strong candidate genes; proteomic studies of the patient's serum and bronchoalveolar lavage fluid and gene expression analyses of her cells were consistent with dysregulation of the tumor necrosis factor-alpha pathway. The patient's cultured fibroblasts were incubated with selected drugs, and cell proliferation was inhibited by hydroxychloroquine. Treatment of the patient with hydroxychloroquine conferred prolonged beneficial clinical effects, including stabilization of trismus and reduction of corticosteroid dose, C-reactive protein, and size of masses. This case represents an example of precision medicine applied to discover effective treatments for individuals with enigmatic undiagnosed disorders.
DOI: 10.1016/j.trsl.2019.08.008
PubMed: 31520587
Affiliations:
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Balanda</name><affiliation wicri:level="2"><nlm:affiliation>NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Mason, Christopher E" sort="Mason, Christopher E" uniqKey="Mason C" first="Christopher E" last="Mason">Christopher E. Mason</name><affiliation wicri:level="2"><nlm:affiliation>Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York; The World Quant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, New York; The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York; The World Quant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, New York; The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York</wicri:cityArea></affiliation></author><author><name sortKey="Zumbo, Paul" sort="Zumbo, Paul" uniqKey="Zumbo P" first="Paul" last="Zumbo">Paul Zumbo</name><affiliation wicri:level="2"><nlm:affiliation>Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Physiology and Biophysics, Weill Cornell Medicine, New York</wicri:cityArea></affiliation></author><author><name sortKey="Evans, Colleen A" sort="Evans, Colleen A" uniqKey="Evans C" first="Colleen A" last="Evans">Colleen A. Evans</name><affiliation wicri:level="2"><nlm:affiliation>NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Van Waes, Carter" sort="Van Waes, Carter" uniqKey="Van Waes C" first="Carter" last="Van Waes">Carter Van Waes</name><affiliation wicri:level="2"><nlm:affiliation>Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthBethesda, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthBethesda</wicri:cityArea></affiliation></author><author><name sortKey="Gahl, William A" sort="Gahl, William A" uniqKey="Gahl W" first="William A" last="Gahl">William A. Gahl</name><affiliation wicri:level="2"><nlm:affiliation>Section of Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Section of Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Malicdan, May C V" sort="Malicdan, May C V" uniqKey="Malicdan M" first="May C V" last="Malicdan">May C V. Malicdan</name><affiliation wicri:level="2"><nlm:affiliation>Section of Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Section of Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author></analytic><series><title level="j">Translational research : the journal of laboratory and clinical medicine</title><idno type="eISSN">1878-1810</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Precision medicine has generated diagnoses for many patients with challenging undiagnosed disorders. Some individuals remain without a diagnosis despite comprehensive testing, and this impedes their treatment. This report addresses the role of personalized medicine in identifying effective therapy for an undiagnosed disease. A 22-year-old woman presented with chronic severe recurrent trismus, facial pain, progressive multicentric inflammatory and fibrotic masses, and high C-reactive protein. Sites of disease included the pterygomaxillary region, masseter muscles, mandible, lung, pericardium, intrabdominal cavity, and retroperitoneum. A diagnosis was not established after an extensive assessment, including multiple biopsies. The patient was subsequently evaluated under the Undiagnosed Diseases Program at the National Institutes of Health. Large scale genotyping, proteomic studies, and in vitro and gene expression analyses of fibroblasts obtained from a major disease locus were performed. Germline genetic testing did not identify strong candidate genes; proteomic studies of the patient's serum and bronchoalveolar lavage fluid and gene expression analyses of her cells were consistent with dysregulation of the tumor necrosis factor-alpha pathway. The patient's cultured fibroblasts were incubated with selected drugs, and cell proliferation was inhibited by hydroxychloroquine. Treatment of the patient with hydroxychloroquine conferred prolonged beneficial clinical effects, including stabilization of trismus and reduction of corticosteroid dose, C-reactive protein, and size of masses. This case represents an example of precision medicine applied to discover effective treatments for individuals with enigmatic undiagnosed disorders.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Gochuico, Bernadette R" sort="Gochuico, Bernadette R" uniqKey="Gochuico B" first="Bernadette R" last="Gochuico">Bernadette R. Gochuico</name></region><name sortKey="Balanda, Nicholas J" sort="Balanda, Nicholas J" uniqKey="Balanda N" first="Nicholas J" last="Balanda">Nicholas J. Balanda</name><name sortKey="Evans, Colleen A" sort="Evans, Colleen A" uniqKey="Evans C" first="Colleen A" last="Evans">Colleen A. Evans</name><name sortKey="Gahl, William A" sort="Gahl, William A" uniqKey="Gahl W" first="William A" last="Gahl">William A. Gahl</name><name sortKey="Malicdan, May C V" sort="Malicdan, May C V" uniqKey="Malicdan M" first="May C V" last="Malicdan">May C V. Malicdan</name><name sortKey="Mason, Christopher E" sort="Mason, Christopher E" uniqKey="Mason C" first="Christopher E" last="Mason">Christopher E. Mason</name><name sortKey="Ten, Nicholas S" sort="Ten, Nicholas S" uniqKey="Ten N" first="Nicholas S" last="Ten">Nicholas S. Ten</name><name sortKey="Van Waes, Carter" sort="Van Waes, Carter" uniqKey="Van Waes C" first="Carter" last="Van Waes">Carter Van Waes</name><name sortKey="Ziegler, Shira G" sort="Ziegler, Shira G" uniqKey="Ziegler S" first="Shira G" last="Ziegler">Shira G. Ziegler</name><name sortKey="Zumbo, Paul" sort="Zumbo, Paul" uniqKey="Zumbo P" first="Paul" last="Zumbo">Paul Zumbo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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