Novel Mutations Of Pkhd1 And Ahi1 Identified In Two Families With Cystic Renal Disease

Objective: To report newly identified mutations in two families in China with cystic renal disease. Case presentations: Two fetuses were found by prenatal ultrasound to have symmetrically enlarged kidneys with increased echogenicity and cystic changes. We isolated fetal and parental genomic DNAs from umbilical cord blood and circulating leukocytes, performed next generation sequencing for mutations, followed by Sanger sequencing for confirmation. We discovered two new heterozygous mutations in PKHD1: c.2507_2515delTGAAGGAGG (p.Val836_Glu838del) in exon 24 among the fetus and father, as well as c.6840G>A (p.Trp2280*) in exon 42 among the fetus and mother. A mutation of c.2507_2515delTGAAGGAGG caused deletion of three amino acids. Two heterozygous mutations in AHI1, c.1304G>A (p.Arg435Gln), and c.3257A>G (p.Glu1086Gly) were identified in the second fetus, while the former was also found in the mother. The mutated locus in AHI1 is highly conserved among humans, dogs, mice, and monkeys. Conclusions: We report two newly identified mutations in PKHD1 and AHI1. An accurate genetic diagnosis is crucial for genetic counseling of parents with offspring carrying cystic renal disease.