Fig. 1: WES and targeted sequencing identified heterozygous rare GDF6 variants in three of 194 patients with renal anomalies (1.6%), and in three of 56 patients with renal plus skeletal, ocular or auricular anomalies (5.4%).

a Renal ultrasound of index patient F006.II.1 was notable for left-sided crossed fused kidney (K) ectopia with megaureters (U). b Voiding cystourethrography of patient F006.II.1 revealed grade-IV vesicoureteral reflux into two megaureters (U) with orthotopic ostia in the bladder (B) and connected to the superior or inferior dilated kidney (K) pelvis of the fused kidneys. c, d MRI of the spine of patient F006.II.1 showing malformations of cervical and thoracic vertebral bodies, e.g., fused and butterfly vertebrae (arrows) (c) and missing fifth sacral vertebral body and coccyx (arrow) (d). e, f Renal ultrasound of patient H435.II.1 at the age of 11 years was unremarkable on the right side (e), while the left kidney was hypodysplastic (f) and nonfunctional on DMSA scan. g Renal ultrasound of patient N038.II.1 at age 6 months showing renal hypodysplasia, as indicated by reduced size, hyperechogenicity, and reduced corticomedullary differentiation of the right kidney depicted. The left kidney was also hypodysplastic (not shown), and the patient required kidney transplantation at 5 years of age. h–j Pedigrees of families F006 (h), H435 (i), and N038 (j) with colored shading indicating phenotypical overlap with respect to renal, skeletal, auricular, and ocular anomalies in individuals with rare GDF6 variants. The GDF6 mutational status (V1: c.746C>A p.(Ala249Glu), V2: c.112G>C p.(Gly38Arg), WT: wild-type) is indicated, and corresponding electropherograms are shown for all analyzed family members (no DNA sample was available from individual N038.I.2). Clinical and radiological information was not available from individuals H435.II.3 (1 year of age) or N038.I.2. L, liver; the kidneys are marked by dotted lines (e–g).