American journal of kidney diseases : the official journal of the National Kidney Foundation · 2003
Autosomal recessive Alport's syndrome and benign familial hematuria are collagen type IV diseases.
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Tazón Vega Bárbara, Badenas Cèlia, Ars Elisabet, Lens Xose, Milà Montse, Darnell Alejandro, Torra Roser
Аннотация
BACKGROUND: Alport's syndrome (AS) is a genetically heterogeneous renal hereditary disease. Mutations in collagen type IV genes have been described to be responsible for X-linked (COL4A5), autosomal recessive, and autosomal dominant AS (COL4A3/COL4A4). Moreover, at least 40% of benign familial hematuria (BFH) cases cosegregate with the COL4A3/COL4A4 loci, following a dominant pattern of inheritance. Therefore, it has been suggested that BFH may represent the carrier state for autosomal recessive AS.
METHODS: We report a mutational study of the COL4A3 and COL4A4 genes in 14 AS and 2 BFH families. When possible, linkage analysis has been performed to confirm the pattern of inheritance. One affected proband from each family underwent mutation screening by single-strand conformation polymorphism/heteroduplex analysis.
RESULTS: We identified 13 mutations within the COL4A3 gene and 2 mutations within the COL4A4 gene, 9 of which are first reported here. We also detected 14 polymorphisms within the COL4A3 gene and 15 polymorphisms within the COL4A4 gene, 7 of them not previously described. In 2 of our AS families, we found mutations previously reported for BFH, and we characterized a novel mutation shared by an AS and a BFH family.
CONCLUSION: Collagen type IV nephropathy is an entity in itself, and phenotypic manifestations of COL4A3/COL4A4 mutations may range from monosymptomatic hematuria (BFH) to severe renal failure (AS), depending on the gene dosage. In 3 of our families, we genetically confirmed that BFH represents the carrier state for autosomal recessive AS.
METHODS: We report a mutational study of the COL4A3 and COL4A4 genes in 14 AS and 2 BFH families. When possible, linkage analysis has been performed to confirm the pattern of inheritance. One affected proband from each family underwent mutation screening by single-strand conformation polymorphism/heteroduplex analysis.
RESULTS: We identified 13 mutations within the COL4A3 gene and 2 mutations within the COL4A4 gene, 9 of which are first reported here. We also detected 14 polymorphisms within the COL4A3 gene and 15 polymorphisms within the COL4A4 gene, 7 of them not previously described. In 2 of our AS families, we found mutations previously reported for BFH, and we characterized a novel mutation shared by an AS and a BFH family.
CONCLUSION: Collagen type IV nephropathy is an entity in itself, and phenotypic manifestations of COL4A3/COL4A4 mutations may range from monosymptomatic hematuria (BFH) to severe renal failure (AS), depending on the gene dosage. In 3 of our families, we genetically confirmed that BFH represents the carrier state for autosomal recessive AS.