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Novel ACE mutations mimicking sarcoidosis by increasing blood ACE levels.
Danilov, Sergei M; Jain, Mark S; Petukhov, Pavel A; Goldman, Chananya; DiSanto-Rose, Maria; Vancavage, Rachel; Francuzevitch, Laine Y; Samokhodskaya, Larisa M; Kamalov, Armais A; Arbieva, Zarema H; Sturrock, Edward D; Dudek, Steven M; Judson, Marc A.
Afiliación
  • Danilov SM; Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois; University of Arizona Health Sciences, Tucson, Arizona; Medical Center, Moscow University, Moscow, Russia. Electronic address: danilov@uic.edu.
  • Jain MS; Medical Center, Moscow University, Moscow, Russia.
  • Petukhov PA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois.
  • Goldman C; Division of Pulmonary and Critical Care Medicine, Albany Medical College, Albany, New York.
  • DiSanto-Rose M; Division of Pulmonary and Critical Care Medicine, Albany Medical College, Albany, New York.
  • Vancavage R; Division of Pulmonary and Critical Care Medicine, Albany Medical College, Albany, New York.
  • Francuzevitch LY; Medical Center, Moscow University, Moscow, Russia; Department of Internal Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; Department of Pulmonology, Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia.
  • Samokhodskaya LM; Medical Center, Moscow University, Moscow, Russia.
  • Kamalov AA; Medical Center, Moscow University, Moscow, Russia.
  • Arbieva ZH; Research Resource Center, University of Illinois at Chicago, Chicago, Illinois.
  • Sturrock ED; Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular, Medicine, University of Cape Town, Cape Town, South Africa.
  • Dudek SM; Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.
  • Judson MA; Division of Pulmonary and Critical Care Medicine, Albany Medical College, Albany, New York.
Transl Res ; 230: 5-20, 2021 04.
Article en En | MEDLINE | ID: mdl-32726712
An elevated blood angiotensin I-converting enzyme (ACE) supports diagnosis of sarcoidosis and Gaucher disease. However, some ACE mutations increase ACE shedding, and patients with these mutations are therefore at risk of being incorrectly diagnosed with sarcoidosis because of elevated serum ACE levels. We applied a novel approach called "ACE phenotyping" to identify possible ACE mutations in 3 pulmonary clinic patients that had suspected sarcoidosis based on elevated blood ACE levels. Conformational fingerprinting of ACE indicated that these mutations may be localized in the stalk region of the protein and these were confirmed by whole exome sequencing. Index patient 1 (IP1) had a mutation (P1199L) that had been previously identified, while the other 2 patients had novel ACE mutations. IP2 had 2 mutations, T887M and N1196K (eliminating a putative glycosylation site), while IP3 had a stop codon mutation Q1124X (eliminating the transmembrane anchor). We also performed a comprehensive analysis of the existing database of all ACE mutations to estimate the proportion of mutations increasing ACE shedding. The frequency of ACE mutations resulting in increased blood ACE levels may be much higher than previously estimated. ACE phenotyping, together with whole exome sequencing, is a diagnostic approach that could prevent unnecessary invasive and/or costly diagnostic procedures, or potentially harmful treatment for patients misdiagnosed on the basis of elevated blood ACE levels.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo Genético / Sarcoidosis / Peptidil-Dipeptidasa A Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Transl Res Asunto de la revista: MEDICINA / TECNICAS E PROCEDIMENTOS DE LABORATORIO Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo Genético / Sarcoidosis / Peptidil-Dipeptidasa A Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Transl Res Asunto de la revista: MEDICINA / TECNICAS E PROCEDIMENTOS DE LABORATORIO Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos