Spectrum of COL4A5 mutations in Finnish Alport syndrome patients.

Alport syndrome (AS) is a hereditary kidney disorder, mainly caused by mutations in the X-chromosomal gene (COL4A5) encoding the type IV collagen a5 chain. In this study, detection of COL4A5 mutations was performed in 17 Finnish Alport syndrome families. Regions around the 51 previously known exons, as well as the two recently characterized exons 41A and 41B in COL4A5, were PCR-amplified from the patient DNA. Direct sequencing of the amplified products was performed and mutations were found in 12 families. None of the mutations involved exons 41A or 41B. Three of the mutations were potential splicing mutations, two of which were studied at the mRNA level. Seven of the mutations were single base substitutions, and two were deletions. In five families, no mutations were found.

Martin P ，Heiskari N ，Pajari H ，Grönhagen-Riska C ，Kääriäinen H ，Koskimies O ，Tryggvason K ... -  《-》

Alport syndrome. Molecular genetic aspects.

Hertz JM 《-》

Detection of mutations in COL4A5 in patients with Alport syndrome.

Plant KE ，Green PM ，Vetrie D ，Flinter FA ... -  《HUMAN MUTATION》

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 failure, which often is accompanied by sensorineural deafness and ophthalmological signs in the form of anterior lenticonus. The X-linked form of the disease 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-linked cases, 37 cases from families with a pedigree compatible with X-linked inheritance, and 15 isolated cases. We found a mutation detection rate of 52% (42/81) (58% in males and 21% in females), and 69% (20/29) in families who clearly demonstrated X-linked inheritance. Thirty-six different mutations were found in 42 patients comprising 16 missense mutations, seven frameshifts, three in-frame deletions, four nonsense mutations, and six splice site 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 heterozygosity of 28%. Three de novo mutations were found, two of which were paternal and one of maternal origin.

Hertz JM ，Juncker I ，Persson U ，Matthijs G ，Schmidtke J ，Petersen MB ，Kjeldsen M ，Gregersen N ... -  《-》

A two-tier approach to mutation detection in the COL4A5 gene for Alport syndrome.

King K ，Flinter FA ，Green PM 《-》