Genetic mutation analysis of a family with a history of three fetuses with polycystic kidney disease

  Background  Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of end stage renal disease (ESKD). Early genetic diagnosis of patients is helpful to analyze the genetic etiology of patients and family members, and provide fertility guidance to patients and family members.

  Objective  To provide genetic counseling to guide further pregnancy by performing molecular genetic detection on a pregnant woman with three fetuses history of polycystic kidney disease who visited the Obstetrics clinic of the First Medical Center of Chinese PLA General Hospital in April 2021 and her family members.

  Methods  High-throughput sequencing was used to conduct genetic testing of the previously induced labor fetus. The peripheral blood samples of these family members were harvested for DNA extraction. Long-range PCR combined with nested PCR was used to verify these family members, and the genotypes of the pregnant woman and her eldest daughter, her father and her husband were determined before prenatal diagnosis of the amniotic fluid.

  Results  High-throughput sequencing results indicated that there were heterozygous and nonsense mutations of c.7214G>A(p.Trp2405Ter) and missense mutations of c.9884A>G(p.Asn3295Ser) in PKD1 gene of the previously induced labor fetus. The pregnant woman had heterozygous nonsense mutation of c.7214G>A(p.Trp2405Ter), her husband had heterozygous missense mutation of c.9884A>G (p.Asn3295Ser), her father had heterozygous nonsense mutation of c.7214G>A(p.Trp2405Ter). The genetic results of the pregnant woman’s eldest daughter and the induced labor fetus were consistent. Prenatal diagnosis in amniotic fluid specimen found that there were both c.7214G>A(p.Trp2405Ter) heterozygous nonsense mutation and c.9884A>G(p.Asn3295Ser) heterozygous missense mutation in PKD1 gene.

  Conclusion  In this study, it is speculated that the heterozygous mutation of c.7214G>A(p.Trp2405Ter) is a pathogenic mutation site in the family, and the pregnant woman is recommended to undergo detailed fetal kidney ultrasound examination during pregnancy to prevent the birth of child with renal abnormality.