Collagen type IV-related nephropathies in Portugal: pathogenic COL4A3 and COL4A4 mutations and clinical characterization of 25 families

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Sa, MJN (Author) Other; Storey, H (Author) Other; Flinter, F (Author) Other; Nagel, M (Author) Other; Sampaio, S (Author) Other; Castro, R (Author) Other; Araujo, JA (Author) Other; Gaspar, MA (Author) Other; Soares, C (Author) Other; Oliveira, A (Author) Other; Henriques, AC (Author) Other; da Costa, AG (Author) Other; Abreu, CP (Author) Other; Ponce, P (Author) Other; Alves, R (Author) Other; Pinho, L (Author) Other; Silva, SE (Author) Other; Carla Pinto Moura (Author) FMUP; Mendonca, L (Author) Other; Felix Carvalho (Author) FFUP; Pestana M (Author) FMUP; Alves, S (Author) Other; carvalho, f (Author) FMUP; João Paulo Oliveira (Author) FMUP

Journal

Title: Clinical Genetics

Vol. 88

Pages: 456-461

ISSN: 0009-9163

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 15 Citations

Scopus - 21 Citations

Other information

Authenticus ID: P-00G-PWH

DOI: 10.1111/cge.12521

Abstract (EN): Pathogenic mutations in genes COL4A3/COL4A4 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 COL4A3/COL4A4, 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 COL4A3/COL4A4 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 COL4A3/COL4A4 mutations was higher, while the prevalence of XLAS was lower than expected. Overall, a pathogenic COL4A3/COL4A4/COL4A5 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6