ClinVar

Nearly all cases of Alport syndrome (ALS1; 301050) involve distinct mutations, as expected for an X-linked disease that significantly reduces the fitness of affected males. A few COL4A5 mutations appear to be associated with reduced disease severity and may account for an appreciable proportion of late-onset Alport syndrome in populations where a founder effect has occurred. Barker et al. (1997) reported a novel mutation in the COL4A5 gene, R1677Q. It was detected in 3 independently ascertained Ashkenazi-American families, caused a relatively mild form of nephritis with typical onset in the fourth or fifth decade, and may be involved in the etiology of a large proportion of adult-onset hereditary nephritis in Ashkenazi Jews. The mutation was a G-to-A transition in nucleotide 5232 and represented a change at a CpG dinucleotide. The same haplotype of COL4A5-linked markers was found in affected males of the 3 kindreds. No genealogic connection could be established.

Ohkubo et al. (2003) found immunohistochemical evidence that the normal anterior lens capsule expressed all of the A4 collagen chains. They also examined the anterior lens capsule of a patient with Alport syndrome due to the R1677X nonsense mutation. The patient's anterior lenticonus resulted in a lack of immunoreactivity to 4A3 to 4A6 chains in the anterior lens capsule.