A New Point Mutation in the COL4A5 Gene Described in a Spanish Family with X-Linked Alport Syndrome

Abstract

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.

Phacoemulsification and intraocular lens implantation in Alport syndrome with anterior lenticonus

“…The loss of these collagen molecules from the affected basement membranes results in an abnormal ultrastructural appearance. 2,13 The ocular and other clinical features of autosomal recessive Alport syndrome are identical to those seen in the X-linked disease, while retinopathy and cataracts are the only ocular abnormalities described in the rare autosomal dominant form. Hearing problems usually start in childhood in male patients and around 40 years of age in female patients.…”

Biomarkers for osteoarthritis: investigation, identification, and prognosis

“…The presence of “de novo” mutations related to X-linked forms has been previously described 6–8. The pattern of inheritance in the family must be X-linked, since the mutation is located in the COL4A5 gene, the maternal grandmother, patient’s mother and aunt are the paucisymptomatic carriers and the child and two cousins have initiated the disease in childhood and their evolution seems to be fast and progressive.…”

“…More than 300 different mutations have been described 6–8. They are distributed throughout the surface of the COL4A5 gene, and are private (very few families share the same mutation).…”

Alport Syndrome: De Novo Mutation in the COL4A5 Gene Converting Glycine 1205 to Valine

“…2,5 More than 300 different mutations have been described. [6][7][8] They are distributed throughout the surface of the COL4A5 gene, and are private (very few families share the same mutation). 10%-15% are "de novo" mutations in parent's gametes.…”

“…The presence of "de novo" mutations related to X-linked forms has been previously described. [6][7][8] The pattern of inheritance in the family must be X-linked, since the mutation is located in the COL4A5 gene, the maternal grandmother, patient's mother and aunt are the paucisymptomatic carriers and the child and two cousins have initiated the disease in childhood and their evolution seems to be fast and progressive.…”