Mónica Furlano1, Victor Martínez2, Marc Pybus3, Yolanda Arce4, Jaume Crespí5, María Del Prado Venegas6, Gemma Bullich7, Andrea Domingo3, Nadia Ayasreh8, Silvia Benito8, Laura Lorente3, Patricia Ruíz3, Vanesa López Gonzalez9, Rosa Arlandis10, Elisa Cabello11, Ferran Torres12, Lluis Guirado8, Elisabet Ars13, Roser Torra14. 1. Inherited Kidney Diseases, Nephrology Department, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau, Medicine Department-Universitat Autónoma de Barcelona, Red de Investigación Renal, Instituto de Investigación Carlos III, Barcelona, Spain. 2. Nephrology Department, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain. 3. Molecular Biology Laboratory, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau, Universitat Autónoma de Barcelona, Red de Investigación Renal, Instituto de Investigación Carlos III, Barcelona, Spain. 4. Department of Pathology, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau, Universitat Autónoma de Barcelona, Red de Investigación Renal, Instituto de Investigación Carlos III, Barcelona, Spain. 5. Departments of Ophthalmology, Hospital de Sant Pau i la Santa Creu, Instituto de Investigaciones Biomédicas Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain. 6. Otolaryngology-Head and Neck Surgery, Hospital de Sant Pau i la Santa Creu, Instituto de Investigaciones Biomédicas Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain. 7. Centre Nacional d'Anàlisi Genómica, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain. 8. Nephrology Department, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau, Medicine Department-Universitat Autónoma de Barcelona, Red de Investigación Renal, Instituto de Investigación Carlos III, Barcelona, Spain. 9. Genetics Laboratory, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain. 10. Nephrology Department, Hospital General de la Palma, Islas Canarias, Spain. 11. Nephrology Department, Hospital General Universitario de Castellón, Castellón de la Plana, Spain. 12. Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Medical Statistics Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic de Barcelona, Barcelona, Spain. 13. Molecular Biology Laboratory, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau, Universitat Autónoma de Barcelona, Red de Investigación Renal, Instituto de Investigación Carlos III, Barcelona, Spain. Electronic address: ears@fundacio-puigvert.es. 14. Inherited Kidney Diseases, Nephrology Department, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau, Medicine Department-Universitat Autónoma de Barcelona, Red de Investigación Renal, Instituto de Investigación Carlos III, Barcelona, Spain. Electronic address: rtorra@fundacio-puigvert.es.
Abstract
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/1.73m2 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.
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/1.73m2 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.
Authors: Raquel Martínez-Pulleiro; María García-Murias; Manuel Fidalgo-Díaz; Miguel Ángel García-González Journal: Int J Mol Sci Date: 2021-10-14 Impact factor: 5.923
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Authors: Jasmina Ćomić; Korbinian M Riedhammer; Roman Günthner; Christian W Schaaf; Patrick Richthammer; Hannes Simmendinger; Donald Kieffer; Riccardo Berutti; Velibor Tasic; Nora Abazi-Emini; Valbona Nushi-Stavileci; Jovana Putnik; Nataša Stajic; Adrian Lungu; Oliver Gross; Lutz Renders; Uwe Heemann; Matthias C Braunisch; Thomas Meitinger; Julia Hoefele Journal: Front Med (Lausanne) Date: 2022-08-31