Alport syndrome: a unified classification of genetic disorders of collagen IV α345: a position paper of the Alport Syndrome Classification Working Group

Clifford E Kashtan; Jie Ding; Guido Garosi; Laurence Heidet; Laura Massella; Koichi Nakanishi; Kandai Nozu; Alessandra Renieri; Michelle Rheault; Fang Wang; Oliver Gross

doi:10.1016/j.kint.2017.12.018

Alport syndrome: a unified classification of genetic disorders of collagen IV α345: a position paper of the Alport Syndrome Classification Working Group

Kidney Int. 2018 May;93(5):1045-1051. doi: 10.1016/j.kint.2017.12.018. Epub 2018 Mar 16.

Authors

Affiliations

¹ Department of Pediatrics, Division of Pediatric Nephrology, Alport Syndrome Treatments and Outcomes Registry, University of Minnesota Medical School and Masonic Children's Hospital, Minneapolis, Minnesota, USA. Electronic address: kasht001@umn.edu.
² Department of Pediatrics, Peking University First Hospital, Beijing, China.
³ Unita Operativa Complessa Nefrologia, Dialisi e Trapianto, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
⁴ Asssitance Publique-Hôpitaux de Paris, Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte and Service de Néphrologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Paris, France.
⁵ Nephrology and Dialysis Unit, Pediatric Subspecialties Department, Bambino Gesu Children's Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
⁶ Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukus, Okinawa, Japan.
⁷ Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
⁸ Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
⁹ Department of Pediatrics, Division of Pediatric Nephrology, Alport Syndrome Treatments and Outcomes Registry, University of Minnesota Medical School and Masonic Children's Hospital, Minneapolis, Minnesota, USA.
¹⁰ Clinic of Nephrology and Rheumatology, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany.

PMID: 29551517
DOI: 10.1016/j.kint.2017.12.018

Abstract

Mutations in the genes COL4A3, COL4A4, and COL4A5 affect the synthesis, assembly, deposition, or function of the collagen IV α345 molecule, the major collagenous constituent of the mature mammalian glomerular basement membrane. These mutations are associated with a spectrum of nephropathy, from microscopic hematuria to progressive renal disease leading to ESRD, and with extrarenal manifestations such as sensorineural deafness and ocular anomalies. The existing nomenclature for these conditions is confusing and can delay institution of appropriate nephroprotective therapy. Herein we propose a new classification of genetic disorders of the collagen IV α345 molecule with the goal of improving renal outcomes through regular monitoring and early treatment.

Keywords: Alport syndrome; chronic kidney disease; proteinuria.

Publication types

Consensus Development Conference
Research Support, Non-U.S. Gov't

MeSH terms

Autoantigens / genetics*
Collagen Type IV / genetics*
Consensus
DNA Mutational Analysis
Genetic Markers
Genetic Predisposition to Disease
Humans
Mutation*
Nephritis, Hereditary / classification
Nephritis, Hereditary / diagnosis
Nephritis, Hereditary / genetics*
Nephritis, Hereditary / therapy
Phenotype
Predictive Value of Tests
Prognosis
Terminology as Topic*

Substances

Autoantigens
COL4A4 protein, human
COL4A5 protein, human
Collagen Type IV
Genetic Markers
type IV collagen alpha3 chain