Renal hypodysplasia/aplasia 3 caused by a rare variant of GREB1L with incomplete penetrance in a Chinese family.

Renal agenesis (RA) represents the most severe form of congenital anomalies of the kidney and urinary tract (CAKUT). Bilateral renal agenesis (BRA) is almost invariably fatal at birth and has high genetic heterogeneity. Here we report on a Chinese family with two pregnancies affected by a prenatal form of BRA. Trio-WES was conducted to explore the underlying genetic cause and identified a novel nonsense variant (c.2621G>A: p. Trp874Ter) in the GREB1L gene. Based on previous research, pathogenic mutations in GREB1L can cause renal hypodysplasia/aplasia-3 (RHDA3) with autosomal dominant inheritance. Sanger sequencing performed on the family members revealed that the variant was vertically transmitted from the maternal grandfather through the unaffected mother to the two affected fetuses, fully demonstrating the incomplete dominance of the disease. Our study extends the mutational spectrum associated with RHDA3 and contributes to a more general understanding for the complex genetic inheritance of GREB1L.