We can conclude that the only significant difference between the X-linked and the autosomal recessive forms of AS lies in the fact that in the latter females are as affected as males; thus the idea that autosomal recessive AS causes ESRD during childhood must be discarded. Other clinical features such as age of deafness or the presence of post-transplant anti-GBM antibody nephritis show no differences between the entities. Thus an accurate familial study is mandatory in patients with AS, as the identification of the different patterns of inheritance may cause a great difference in genetic counselling. Linkage analysis is the only effective molecular diagnosis that can be performed nowadays.
Background/Aim: Alport syndrome is a hereditary glomerulonephritis, X-linked in 85% of the cases. This form is associated with mutations in the COL4A5 gene which encodes the α5 chain of type IV collagen. We have performed the mutational analysis of the COL4A5 gene in a Spanish family with X-linked Alport syndrome. Methods: We have analyzed three polymorphic markers close to the gene to confirm the X chromosome linkage. By means of the PCR technique, we have screened the 51 exons of the gene. Results: The segregation of the alleles from the analyzed markers was in agreement with the X linkage. Direct sequencing of PCR-amplified products has shown a CCT-to-CTT change in exon 25, resulting in substitution of a proline for a leucine at position 619 of the polypeptide chain (nucleotide 2058). Conclusions: Although proline is considered a nonconserved amino acid, it is essential, upon hydroxylation, in the maintenance of a stable alpha chain triple-helix collagen. Furthermore, the change cosegregates with the disease in all affected members of the family, not being present in 80 control chromosomes. This represents a new mutation in the COL4A5 gene found in the Spanish population.
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