PKHD1 gene mutation analysis in two families of perinatal stage autosomal recessive polycystic kidney disease

Objective To analyze genetic variation in two cases of autosomal recessive polycystic kidney disease （ARPKD） and provide theoretical rationales for its early diagnosis， treatment， genetic counseling and prenatal diagnosis. Methods Fetal tissues and parental peripheral blood samples of two children were collected for whole exon sequencing， pedigree analysis and site verification. Results Whole exome and Sanger sequencing revealed compound heterozygous mutations in c.3436C＞T （p.Q1146X） and c.1981A＞C （p.T661P） in fetal PKHD1 gene in family 1. And one ARPKD child of family 2 previously died of heart failure at the age of 1 year. In this case， c.9719G＞A （p.R3240Q）， c.10057C＞T （p.L3353F） and c.7237C＞T （p.R2413C） compound heterozygous mutations were detected in fetal PKHD1 gene. Conclusion Both families had perinatal stage ARPKD caused by variants in PKHD1 gene and 5 genetic variant loci， including 2 new missense variants of c.10057C＞T and c.1981A＞C. In light of a great complexity of ARPKD genotype and phenotype， early genetic counselling of the pedigree may facilitate genetic diagnosis and early prenatal diagnosis.