[The power of linkage analysis on PAH gene in prenatal gene diagnosis is improved with three additional short tandem repeat markers].

OBJECTIVE To increase the success rate of prenatal diagnosis for classical phenylketonuria(PKU). METHODS Three new short tandem repeat (STR) markers (PAH26, PAH32 and PAH9) within and surrounding phenylalanine hydroxylase(PAH) gene were selected for amplified fragment length polymorphism. The allele frequencies and polymorphism information contests (PIC) were determined in Chinese population. RESULTS The PIC of these three new STR markers was 0.518 (PAH26), 0.413 (PAH32) and 0.362 (PAH9) respectively. There was linkage disequilibrium between PAH9 marker and PAH-STR marker (TCTA)n in the intron 3 of PAH gene. The linkage phase of the mutant genes and the markers was established using the combination of PAH-STR, PAH26 and PAH32 in 95% families. Prenatal diagnosis was performed successfully with these markers in four cases. CONCLUSION By selecting or combining the three STR markers, the mutant genes could be distinguished from the normal allele in up to 95% of families with classical PKU.