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Detection of mutations in the COL4A5 gene by SSCP in X‐linked Alport syndrome
Author(s) -
Hertz Jens Michael,
Juncker Inger,
Persson Ulf,
Matthijs Gert,
Schmidtke Jörg,
Petersen Michael B.,
Kjeldsen Margrethe,
Gregersen Niels
Publication year - 2001
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1163
Subject(s) - alport syndrome , genetics , missense mutation , biology , exon , frameshift mutation , nonsense mutation , mutation , gene , x linked recessive inheritance , hum , x chromosome , microbiology and biotechnology , glomerulonephritis , art , performance art , art history , kidney
Abstract 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 α5‐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. Hum Mutat 18:141–148, 2001. © 2001 Wiley‐Liss, Inc.