Clinical and Genetic Features of Autosomal Dominant Alport Syndrome

Rationale & Objective: Alport syndrome is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in the gene COL4A3, COL4A4, or COL4A5. The aim of this study was to evaluate the clinical and gene...

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Detalles Bibliográficos
Autores: Furlano, Monica|||0000-0003-1025-3901, Martínez, Victor, Pybus, Marc|||0000-0002-6195-5738, Arce, Yolanda, Crespí, Jaume|||0000-0001-7564-2479, Venegas, María del Prado|||0000-0001-9048-4501, Bullich Vilanova, Gemma|||0000-0002-0737-4422, Domingo, Andrea|||0000-0003-3759-7595, Ayasreh Fierro, Nadia|||0000-0001-6436-5621, Benito, Silvia, Lorente, Laura, Ruíz, Patricia, Gonzalez, Vanesa L., Arlandis, Rosa, Cabello, Elisa, Torres, Ferran|||0000-0002-7355-7913, Guirado, Luis|||0000-0001-5119-3912, Ars, Elisabet|||0000-0002-4118-4358, Torra Balcells, Roser|||0000-0001-8714-2332
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:269618
Acceso en línea:https://ddd.uab.cat/record/269618
https://dx.doi.org/urn:doi:10.1053/j.ajkd.2021.02.326
Access Level:acceso abierto
Palabra clave:Alport syndrome
Autosomal-dominant Alport syndrome
COL4A3
COL4A4
Familial benign hematuria
Familial hematuria
Genetic
Genotype-phenotype correlation
Hearing loss
Hereditary kidney disease
Inherited kidney disease
Thin basement membrane disease
Descripción
Sumario:Rationale & Objective: Alport syndrome is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in the gene COL4A3, COL4A4, or COL4A5. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS). Study Design: Retrospective cohort study. Setting & Participants: 82 families (252 patients) with ADAS were studied. Clinical, genetic, laboratory, and pathology data were collected. Observations: A pathogenic DNA variant in COL4A3 was identified in 107 patients (35 families), whereas 133 harbored a pathogenic variant in COL4A4 (43 families). Digenic/complex inheritance was observed in 12 patients. Overall, the median kidney survival was 67 (95% CI, 58-73) years, without significant differences across sex (P = 0.8), causative genes (P = 0.6), or type of variant (P = 0.9). Microhematuria was the most common kidney manifestation (92.1%), and extrarenal features were rare. Findings on kidney biopsies ranged from normal to focal segmental glomerulosclerosis. The slope of estimated glomerular filtration rate change was -1.46 (-1.66 to -1.26) mL/min/1.73 m per year for the overall group, with no significant differences between ADAS genes (P = 0.2). Limitations: The relatively small size of this series from a single country, potentially limiting generalizability. Conclusions: Patients with ADAS have a wide spectrum of clinical presentations, ranging from asymptomatic to kidney failure, a pattern not clearly related to the causative gene or type of variant. The diversity of ADAS phenotypes contributes to its underdiagnosis in clinical practice.

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