What Is Hidden in Patients with Unknown Nephropathy? Genetic Screening Could Be the Missing Link in Kidney Transplantation Diagnosis and Management
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Published:2024-01-24
Issue:3
Volume:25
Page:1436
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Mitrotti Adele1, Di Bari Ighli1, Giliberti Marica1, Franzin Rossana1ORCID, Conserva Francesca1ORCID, Chiusolo Anna1, Gigante Maddalena1ORCID, Accetturo Matteo1, Cafiero Cesira1, Ricciato Luisa1, Stea Emma Diletta1, Forleo Cinzia1ORCID, Gallone Anna2ORCID, Rossini Michele1, Fiorentino Marco1ORCID, Castellano Giuseppe34, Pontrelli Paola1ORCID, Gesualdo Loreto1
Affiliation:
1. Department of Precision and Regenerative Medicine and Ionian Area (DIMEPRE-J), University of Bari Aldo Moro, 70124 Bari, Italy 2. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, 70121 Bari, Italy 3. Department of Clinical Sciences and Community Health, University of Milano, 20122 Milano, Italy 4. Fondazione IRCCS Cà Grande Ospedale Maggiore Policlinico, 20122 Milano, Italy
Abstract
Between 15–20% of patients with end stage renal disease (ESRD) do not know the cause of the primary kidney disease and can develop complications after kidney transplantation. We performed a genetic screening in 300 patients with kidney transplantation, or undiagnosed primary renal disease, in order to identify the primary disease cause and discriminate between overlapping phenotypes. We used a custom-made panel for next-generation sequencing (Agilent technology, Santa Clara, CA, USA), including genes associated with Fabry disease, podocytopaties, complement-mediated nephropathies and Alport syndrome-related diseases. We detected candidate diagnostic variants in genes associated with nephrotic syndrome and Focal Segmental Glomerulosclerosis (FSGS) in 29 out of 300 patients, solving about 10% of the probands. We also identified the same genetic cause of the disease (PAX2: c.1266dupC) in three family members with different clinical diagnoses. Interestingly we also found one female patient carrying a novel missense variant, c.1259C>A (p.Thr420Lys), in the GLA gene not previously associated with Fabry disease, which is in silico defined as a likely pathogenic and destabilizing, and associated with a mild alteration in GLA enzymatic activity. The identification of the specific genetic background may provide an opportunity to evaluate the risk of recurrence of the primary disease, especially among patient candidates living with a donor kidney transplant.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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