Spectrum of COL4A5 mutations in Finnish Alport syndrome patients

Abstract

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. Hum Mutat 15:579, 2000. © 2000 Wiley‐Liss, Inc.

Screening of Living Kidney Donors for Genetic Diseases Using a Comprehensive Genetic Testing Strategy

“…Genetic testing identified a splice site mutation in intron 38 of COL4A5 (3657‐9A>G). This variant has been reported as pathogenic, confirming X‐linked Alport syndrome . The 35‐year‐old sister had negative urinalysis and a negative slit lamp examination and was negative for the splicing mutation.…”

Screening of Living Kidney Donors for Genetic Diseases Using a Comprehensive Genetic Testing Strategy

“…Genetic testing identified a splice site mutation in intron 38 of COL4A5 (3657‐9A>G). This variant has been reported as pathogenic, confirming X‐linked Alport syndrome . The 35‐year‐old sister had negative urinalysis and a negative slit lamp examination and was negative for the splicing mutation.…”

Detection of large deletion mutations in the COL4A5 gene of female Alport syndrome patients

“…Most mutational analyses of COL4A5 in XLAS patients are based on genomic DNA analysis, for a mutation detection rate of 31% to 82% [4,6,8,[10][11][12][14][15][16][17][18]. Recently, the detection level has slightly improved with the introduction of reverse transcriptase-polymerase chain reaction (RT-PCR) using mRNA extracted from hair roots [3,5], skin fibroblasts [7] or leukocytes [13], for a current detection rate of 77% to 84%, which, however, is still not satisfactory.…”

“…The overall detection rate of COL4A5 gene mutations in XLAS cases remains 37% to 84% [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] and as low as 20% to 71% for female patients only [3,8,10,13], thus showing a clear discrepancy in mutation detection rate between the genders. This also indicated that there may be some problem with the use of conventional methods for mutational analysis of COL4A5.…”

Two novel alternatively spliced 9-bp exons in the COL4A5 gene

“…All the 36 patients (20 males/16 females) had been previously analyzed for mutations in the COL4A5 gene, and shown not to have sequence variations in any of the 51 exons. Based on clinical data (available for 14 males and 6 females), 5 patients were suspected of having the autosomal recessive form of Alport syndrome [9,12].…”

Screening of Living Kidney Donors for Genetic Diseases Using a Comprehensive Genetic Testing Strategy

“…Genetic testing identified a splice site mutation in intron 38 of COL4A5 (3657‐9A>G). This variant has been reported as pathogenic, confirming X‐linked Alport syndrome . The 35‐year‐old sister had negative urinalysis and a negative slit lamp examination and was negative for the splicing mutation.…”

Detection of large deletion mutations in the COL4A5 gene of female Alport syndrome patients

“…Most mutational analyses of COL4A5 in XLAS patients are based on genomic DNA analysis, for a mutation detection rate of 31% to 82% [4,6,8,[10][11][12][14][15][16][17][18]. Recently, the detection level has slightly improved with the introduction of reverse transcriptase-polymerase chain reaction (RT-PCR) using mRNA extracted from hair roots [3,5], skin fibroblasts [7] or leukocytes [13], for a current detection rate of 77% to 84%, which, however, is still not satisfactory.…”

“…The overall detection rate of COL4A5 gene mutations in XLAS cases remains 37% to 84% [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] and as low as 20% to 71% for female patients only [3,8,10,13], thus showing a clear discrepancy in mutation detection rate between the genders. This also indicated that there may be some problem with the use of conventional methods for mutational analysis of COL4A5.…”

Two novel alternatively spliced 9-bp exons in the COL4A5 gene

“…All the 36 patients (20 males/16 females) had been previously analyzed for mutations in the COL4A5 gene, and shown not to have sequence variations in any of the 51 exons. Based on clinical data (available for 14 males and 6 females), 5 patients were suspected of having the autosomal recessive form of Alport syndrome [9,12].…”

Screening of Living Kidney Donors for Genetic Diseases Using a Comprehensive Genetic Testing Strategy

“…Genetic testing identified a splice site mutation in intron 38 of COL4A5 (3657‐9A>G). This variant has been reported as pathogenic, confirming X‐linked Alport syndrome . The 35‐year‐old sister had negative urinalysis and a negative slit lamp examination and was negative for the splicing mutation.…”

Detection of large deletion mutations in the COL4A5 gene of female Alport syndrome patients

“…Most mutational analyses of COL4A5 in XLAS patients are based on genomic DNA analysis, for a mutation detection rate of 31% to 82% [4,6,8,[10][11][12][14][15][16][17][18]. Recently, the detection level has slightly improved with the introduction of reverse transcriptase-polymerase chain reaction (RT-PCR) using mRNA extracted from hair roots [3,5], skin fibroblasts [7] or leukocytes [13], for a current detection rate of 77% to 84%, which, however, is still not satisfactory.…”

“…The overall detection rate of COL4A5 gene mutations in XLAS cases remains 37% to 84% [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] and as low as 20% to 71% for female patients only [3,8,10,13], thus showing a clear discrepancy in mutation detection rate between the genders. This also indicated that there may be some problem with the use of conventional methods for mutational analysis of COL4A5.…”

Two novel alternatively spliced 9-bp exons in the COL4A5 gene

“…All the 36 patients (20 males/16 females) had been previously analyzed for mutations in the COL4A5 gene, and shown not to have sequence variations in any of the 51 exons. Based on clinical data (available for 14 males and 6 females), 5 patients were suspected of having the autosomal recessive form of Alport syndrome [9,12].…”