ClinVar

In all affected members of a 3-generation family with renal agenesis and/or uterovaginal agenesis (RHDA3; 617805), Herlin et al. (2019) identified heterozygosity for a c.705G-T transversion (c.705G-T, NM_001142966) in the GREB1L gene, resulting in a trp235-to-cys (W235C) substitution at a highly conserved residue. The mutation, which was not found in the gnomAD database, was present in 2 unaffected sisters (II-2 and II-4) who had inherited it from their affected father (I-3) and transmitted it to their affected offspring (III-1, III-2, III-3, and III-5), suggesting that the variant is penetrant only when maternally inherited. However, their brother (II-5), who also carried the mutation and had transmitted it to an unaffected daughter, had multicystic kidney disease. The authors suggested that the latter was an independent finding with no association to GREB1L; thus the pedigree would represent autosomal dominant inheritance with incomplete penetrance in a parent-origin-specific manner, possibly due to imprinting.