Genetic analysis and prenatal diagnosis of a phenylketonuria pedigree

Objective To provide genetic counselling for a pregnant with phenylketonuria (PKU) family history. To provide prenatal diagnosis for the pregnant of the pedigree, followed by identifying of the pathogenic mutation of the proband and the genotype of the other family members. Methods Sanger sequencing was performed to detect the phenylalanine hydroxylase (PAH) gene pathogenic mutation of the patient. Both sequencing and haplotype of the short tandem repeats (STR) site in intron 3 were analyzed for the fetus, whose mother was the aunt of the patient. Results Compound heterozygote mutation of PAH gene, IVS4-1G>A /c.770G>T was identified for the proband, which inherited from his father and mother respectively. The aunt of the patient was a carrier of the IVS4-1G>A heterozygote mutation, whose husband was identified c. 827T>A heterozygote mutation. Prenatal diagnosis disclosed that the fetus inherited the paternal c. 827T>A mutation, and the haplotype of the PAH gene was different from the patient. Conclusion According to the counselling of autosomal recessive disorder, for the partner of a carrier, it is suggested that mutation detection should be performed to exclude the possibility of being a carrier too, and then the risk of the offspring can be evaluated precisely.(Chin J Lab Med, 2018, 41: 312-315) Key words: Phenylketonuria; PAH gene; Mutation; Prenatal diagnosis