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Alport syndrome (AS) is a progressive renal disease characterized by haematuria and progressive renal failure. An accurate genetic diagnosis of AS is very important for genetic counselling and even prenatal diagnosis. We detected mutation of COL4An by amplifying the entire coding sequence mRNA of peripheral blood lymphocytes using polymerase chain reaction (PCR) in five Chinese AS families who asked for genetic counselling and prenatal diagnosis, then performed prenatal genetic diagnosis for four families. Mutation analysis of the foetus was made using DNA extracted from amniocytes. Foetus sex was determined by PCR amplification of SRY as well as karyotype analysis. Maternal cell contamination was excluded by linkage analysis. Four different COL4A5 gene variants and two COL4A3 gene variants were detected in the five families. Because there was a de novo mutation in family 2, prenatal diagnosis was performed for the other four families. Results showed a normal male foetus for family 1 and family 4, respectively. Results showed an affected male foetus for families 3 and 5, and the pregnancies were terminated. An easier, faster and efficacious method for COL4An gene mutation screening based on mRNA analysis from peripheral blood lymphocytes was established. Prenatal genetic diagnosis was performed in four AS families in China. Prenatal genetic diagnosis was performed in Alport syndrome families in China. A rapid and efficacious method for screening of the COL4An gene mutation for Alport syndrome is presented, based on mRNA analysis from peripheral blood lymphocytes. [ABSTRACT FROM AUTHOR]

Alport syndrome (AS) is a progressive renal disease characterized by hematuria and progressive renal failure. X-linked dominant AS (XLAS) is the major inheritance form, accounting for almost 80 of the cases, caused by mutations in COL4A5gene. An accurate genetic diagnosis of AS is very important for genetic counseling and even prenatal diagnosis. In this study we detected mutation of COL4A5by amplifying the entire coding sequence mRNA of peripheral blood lymphocytes using nested PCR in a Chinese XLAS family, and then performed the first prenatal diagnosis of AS in China. Mutation analysis of the fetus was performed on both cDNA-based level and DNA-based level of amniocytes. Fetus sex was determined by PCR amplification of SRYand karyotypes analysis. Maternal cell contamination was excluded by linkage analysis. There was a G-to-A substitution at position 4271 in exon 46 of COL4A5gene (c.G4271A) in the pregnant woman; this genetic variant has not been described previously and was a novel missense mutation. The fetus did not carry the same mutation as the mother. PCR amplification product of SRYand karyotypes analysis revealed a male fetus. Linkage analysis showed that there was no contamination of maternal cells in amniocytes. [ABSTRACT FROM AUTHOR]