Mutational analysis of COL4A5 gene in Korean Alport syndrome

Mutational analysis of the COL4A5 gene in X-linked Alport syndrome (AS) req uires an expensive and time-consuming procedure with a detection rate of 50 %, at best. There have been three multicenter collaborative studies of muta tion analysis in the COL4A5 gene using systematic screening of entire codin g regions of the gene. This is a similar study executed in a single center in Korea, Twenty-five unrelated Korean patients with AS in whom the diagnos is was confirmed pathologically were included in the study. By systematic s creening of all 51 exons of the gene using polymerase chain reaction/single -strand conformation polymorphism analysis, ten mutations were detected in 10 unrelated patients. These included one medium-sized deletion involving e xon 49-51, one single base pair deletion, one nonsense point mutation, one splice site mutation, and six missense point mutations. Of the six missense mutations, four involved a glycine residue and disrupted the Gly-X-Y repea ts in the collagenous domain. The overall detection rate of mutations was 4 0%. Although DNA analysis in AS is currently not applicable to routine clin ical diagnosis due to several practical and technical problems, it is likel y to replace morphological diagnosis in the near future.