Detection of mutations in the COL4A5 gene by SSCP in X-linked Alport syndrome

Alport syndrome is a progressive renal disease leading to chronic renal fai lure, which often is accompanied by sensorineural deafness and ophthalmolog ical signs in the form of anterior lenticonus. The X-linked form of the dis ease is caused by mutations in the COL4A5 gene encoding the alpha5-chain of type IV-collagen. We performed mutation analysis of the COL4A5 gene by PCR , SSCP analysis of each of the 51 exons with flanking intronic sequences in 81 patients suspected of X-linked Alport syndrome including 29 clear X-lin ked cases, 37 cases from families with a pedigree compatible with X-linked inheritance, and 15 isolated cases. We found a mutation detection rate of 5 2% (42/81) (58% in males and 21% in females), and 69% (20/29) in families w ho clearly demonstrated X-linked inheritance. Thirty,six different mutation s were found in 42 patients comprising 16 missense mutations, seven framesh ifts, three in-frame deletions, four nonsense mutations, and six splice sit e mutations. Twenty,two of the mutations have not previously been reported. Furthermore, we found one non-pathogenic amino acid substitution, one rare variant in a non, coding region, and one polymorphism with a heterozygosit y of 28%. Three de novo mutations were found, two of which were paternal an d one of maternal origin. Hum Mutat 18:141-148, 2001. (C) 2001 Wiley-Liss, Inc.