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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

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

Revista

Título: Clinical Genetics

Vol. 88

Páginas: 456-461

ISSN: 0009-9163

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 15 Citações

Scopus - 21 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 6