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

被引:34
作者
Hertz, JM
Juncker, I
Persson, U
Matthijs, G
Schmidtke, J
Petersen, MB
Kjeldsen, M
Gregersen, N
机构
[1] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus C, Denmark
[2] Univ Lund Hosp, Dept Nephrol, S-22185 Lund, Sweden
[3] Univ Leuven, Ctr Human Genet, Lab Mol Diag, Louvain, Belgium
[4] Hannover Med Sch, Inst Human Genet, D-3000 Hannover, Germany
[5] Aghia Sophia Childrens Hosp, Inst Child Hlth, Dept Genet, Athens, Greece
[6] Aarhus Univ Hosp, Res Unit Mol Med, Aarhus N, Denmark
[7] Fac Hlth Sci, Ctr Med Mol Biol, Aarhus N, Denmark
关键词
Alport syndrome; AS; hereditary nephritis; COL4A5; SSCP; collagen; type-IV; mutation detection;
D O I
10.1002/humu.1163
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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. Hum Mutat 18:141-148, 2001. (C) 2001 Wiley-Liss, Inc.
引用
收藏
页码:141 / 148
页数:8
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