Mutation detection of COL4An gene based on mRNA of peripheral blood lymphocytes and prenatal diagnosis of Alport syndrome in China.

AIM: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.