This website provides compact information on patients with variants in the GDF6 gene, including clinical data, genetic and other molecular data, management and research options with the aim to improve patient management.

GDF6 encodes a BMP/TGF-β family ligand that signals through BMP/TGF-β receptors and SMAD activation and is known for its pleiotropic roles in skeletal and ocular development. Variants in the GDF6 gene are associated with various phenotypes, i.e. (i) Klippel-Feil syndrome (KFS) with vertebral segmentation defects frequently associated with scoliosis, rib anomalies, and Sprengel’s deformity now known as KFS1, (ii) Chiari malformations, (iii) multiple synostoses syndrome including carpal and tarsal fusions, and (iv) ocular phenotypes, i.e. microphthalmia, coloboma, Leber congenital amaurosis or juvenile retinitis pigmentosa, and glaucoma. Recent evidence has expanded the phenotypic spectrum to congenital anomalies of the kidney and urinary tract (CAKUT). In a cohort study, rare heterozygous GDF6 variants were identified in patients with crossed fused renal ectopia and kidney hypodysplasia, often accompanied by vertebral, ocular, or auricular anomalies. GDF6 expression was shown in the infant human kidney, the developing murine kidney and the pronephros development in Xenopus laevis. Functional analyses demonstrated that loss of Gdf6 impairs migration of murine collecting duct cells in vitro and pronephros development in Xenopus laevis, supporting a role in nephrogenesis.

Not all individuals with a variant in the GDF6 gene have these features.

Dr. rer. nat. Helge Martens, Department of Human Genetics, Hannover Medical School, Hannover, Germany, Martens.Helge@mh-hannover.de
Dr. med. habil. Ruthild G. Weber, Department of Human Genetics, Hannover Medical School, Hannover, Germany, Weber.Ruthild@mh-hannover.de