Collagen type IV‐related nephropathies in Portugal: pathogenic COL4A3 and COL4A4 mutations and clinical characterization of 25 families. (10th November 2014)

• Record Type: Journal Article
• Authors: Nabais Sá, M.J.; Storey, H.; Flinter, F.; Nagel, M.; Sampaio, S.; Castro, R.; Araújo, J.A.; Gaspar, M.A.; Soares, C.; Oliveira, A.; Henriques, A.C.; da Costa, A.G.; Abreu, C.P.; Ponce, P.; Alves, R.; Pinho, L.; Silva, S.E.; de Moura, C.P.; Mendonça, L.; Carvalho, F.; Pestana, M.; Alves, S.; Carvalho, F.; Oliveira, J.P.
• Is Part Of: Clinical genetics. Volume 88:Number 5(2015:Nov.)
• Page Start: 456
• Page End: 461
• Publication Date: 2014-11-10
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12521
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12521-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12521-para-0001">Pathogenic mutations in genes <italic>COL4A3/COL4A4</italic> are responsible for autosomal Alport syndrome (AS) and thin basement membrane nephropathy (TBMN). We used Sanger sequencing to analyze all exons and splice site regions of <italic>COL4A3</italic>/<italic>COL4A4</italic>, in 40 unrelated Portuguese probands with clinical suspicion of AS/TBMN. To assess genotype–phenotype correlations, we compared clinically relevant phenotypes/outcomes between homozygous/compound heterozygous and apparently heterozygous patients. Seventeen novel and four reportedly pathogenic <italic>COL4A3/COL4A4</italic> mutations were identified in 62.5% (25/40) of the probands. Regardless of the mutated gene, all patients with ARAS manifested chronic renal failure (CRF) and hearing loss, whereas a minority of the apparently heterozygous patients had CRF or extrarenal symptoms. CRF was diagnosed at a significantly younger age in patients with ARAS. In our families, the occurrence of <italic>COL4A3</italic>/<italic>COL4A4</italic> mutations was higher, while the prevalence of XLAS was lower than expected. Overall, a pathogenic <italic>COL4A3</italic>/<italic>COL4A4</italic>/<italic>COL4A5</italic> mutation was identified in >50% of patients with fewer than three of the standard diagnostic criteria of AS. With such a population background, simultaneous next‐generation sequencing of all three genes may be recommended as the most expedite approach to diagnose collagen IV‐related glomerular basement membrane nephropathies.</p> </abstract>