A mutation in the SAA1 promoter causes hereditary amyloid A amyloidosis.

Autor:	Sikora J; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic; Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic., Kmochová T; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic., Mušálková D; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic., Pohludka M; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic., Přikryl P; Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic., Hartmannová H; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic., Hodaňová K; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic., Trešlová H; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic., Nosková L; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic., Mrázová L; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic., Stránecký V; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic., Lunová M; Institute for Clinical and Experimental Medicine, Prague, Czech Republic., Jirsa M; Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic., Honsová E; Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic; AeskuLab Pathology, Prague, Czech Republic., Dasari S; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA., McPhail ED; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., Leung N; Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA., Živná M; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic., Bleyer AJ; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic; Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA., Rychlík I; Department of Medicine, Third Faculty of Medicine, Charles University in Prague and Faculty Hospital Kralovske Vinohrady, Prague, Czech Republic., Ryšavá R; Department of Nephrology, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic. Electronic address: Romana.Rysava@vfn.cz., Kmoch S; Research Unit for Rare Diseases, Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General Teaching Hospital in Prague, Prague, Czech Republic; Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. Electronic address: skmoch@lf1.cuni.cz.
Jazyk:	angličtina
Zdroj:	Kidney international [Kidney Int] 2022 Feb; Vol. 101 (2), pp. 349-359. Date of Electronic Publication: 2021 Sep 21.
DOI:	10.1016/j.kint.2021.09.007
Abstrakt:	Amyloid A amyloidosis is a serious clinical condition resulting from the systemic deposition of amyloid A originating from serum amyloid A proteins with the kidneys being the most commonly and earliest affected organ. Previously described amyloid A amyloidosis is linked to increased production and deposition of serum amyloid A proteins secondary to inflammatory conditions arising from infectious, metabolic, or genetic causes. Here we describe a family with primary amyloid A amyloidosis due to a chr11:18287683 T>C (human genome version19) mutation in the SAA1 promoter linked to the amyloidogenic SAA1.1 haplotype. This condition leads to a doubling of the basal SAA1 promoter activity and sustained elevation of serum amyloid A levels that segregated in an autosomal dominant pattern in 12 genetically affected and in none of six genetically unaffected relatives, yielding a statistically significant logarithm of odds (LOD) score over 5. Affected individuals developed proteinuria, chronic kidney disease and systemic deposition of amyloid composed specifically of the SAA1.1 isoform. Tocilizumab (a monoclonal antibody against the interleukin-6 receptor) had a beneficial effect when prescribed early in the disease course. Idiopathic forms represent a significant and increasing proportion (15-20%) of all diagnosed cases of amyloid A amyloidosis. Thus, genetic screening of the SAA1 promoter should be pursued in individuals with amyloid A amyloidosis and no systemic inflammation, especially if there is a positive family history. (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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