Biallelic PKD1 mutations causing neonatal death in an extremely preterm infant: a Korean case report of very early-onset ADPKD.

backgroundVery early-onset autosomal dominant polycystic kidney disease (VEO-ADPKD) caused by biallelic PKD1 mutations is extremely rare and often phenocopies autosomal recessive PKD (ARPKD), complicating prenatal diagnosis and genetic counseling. CASE PRESENTATION: We report an extremely preterm Korean male infant (27 + 3 weeks, 1300 g) with fetal polycystic kidney disease and severe oligohydramnios from 24 + 6 weeks. The infant died on day 2 with refractory hypoxemia despite maximal support. Clinical exome sequencing revealed compound heterozygous PKD1 variants: a paternally inherited truncating variant (c.11343 C > A, p.Tyr3781Ter) and a maternally inherited non-truncating hypomorphic variant (c.3876 C > A, p.Phe1292Leu). Segregation analysis confirmed trans configuration and identified paternal somatic mosaicism (imbalanced heterozygous peaks on Sanger sequencing), accounting for the phenotypic discordance between the infant's lethal presentation and the father's mild disease at age 31. No pathogenic variants were identified in PKHD1, PKD2, or other cystic kidney disease genes.

conclusionsThis first Korean case demonstrates that biallelic PKD1 mutations cause neonatal-lethal disease that mimics ARPKD via gene-dosage effects, with parental mosaicism creating unpredictable recurrence risks. Genomic autopsy enabled an accurate diagnosis and strongly supports preimplantation genetic testing for this couple.