RT info:eu-repo/semantics/article
T1 COL4A4 gene study of a European population: description of new mutations causing autosomal dominant Alport syndrome
A1 Rosado, Consolación
A1 Bueno Martínez, Elena
A1 Felipe, Carmen
A1 González Sarmiento, Rogelio
K1 Autosomal alport syndrome
K1 COL4A4
K1 Gene
K1 24 Ciencias de la Vida
AB Background: Autosomal forms of Alport syndrome represent 20% of all patients (15% recessive and 5% dominant). They are caused by mutations in the COL4A3 and COL4A4 genes, which encode a-3 and a-4 collagen IV chains of the glomerular basement membrane, cochlea and eye. Thin basement membrane nephropathy may affect up to 1% of the population. The pattern of inheritance in the 40% of cases is the same as autosomal dominant Alport syndrome: heterozygous mutations in these genes. The aim of this study is to detect new pathogenic mutations in the COL4A4 gene in the patients previously diagnosed with autosomal Alport syndrome and thin basement membrane nephropathy in our hospital. Methods: We conducted a clinical and genetic study in eleven patients belonging to six unrelated families with aforementioned clinical symptoms and a negative study of COL4A3 gene. The molecular study was made by conformation of sensitive gel electrophoresis (CSGE) and direct sequencing of the fragments that show an altered electrophoretic migration pattern. Results: We found two pathogenic mutations, not yet described: IVS3 + 1G > C is a replacement of Guanine to Cytosine in position +1 of intron 3, in the splicing region, which leads to a pathogenic mutation. c.4267C > T; p.P1423S is a missense mutation, also considered pathogenic. We also found seven new polymorphisms. Conclusions: We describe two new pathogenic mutations, responsible for autosomal dominant Alport syndrome. The other families of the study were undiagnosed owing to problems in the method employed and the possibility of mutations in other genes, giving rise to other diseases with similar symptoms
PB e-Century Publishing
SN 1948-1756
YR 2014
FD 2014
LK https://uvadoc.uva.es/handle/10324/47503
UL https://uvadoc.uva.es/handle/10324/47503
LA eng
NO International Journal of Molecular Epidemiology and Genetics, 2014, vol. 5, n. 4, p. 177–184
NO Producción Científica
DS UVaDOC
RD 23-may-2024