Fig. 1. Identification of PPARγ2 E379K and R212Q.

a Family pedigree of index patient 1. Each family member is numbered for identification. The proband is indicated by an arrow. Squares and circles indicate males and females, respectively. Phenotypes are elaborated by color segments showing the presence of specific features. Gray symbols denote individuals that were not available for DNA analysis. Deceased individuals are indicated by a diagonal line through the symbol. DNA sequence analysis showing the heterozygous E379K mutation. The chromatogram shows both alleles from the patient (left panel) in comparison with corresponding genomic DNA from a non-affected individual (right panel). For tracing, the nucleotide and amino acid sequences are shown. b Family pedigree of index patient 2, harboring a heterozygous R212Q mutation. See description of panel a for details on representation. c Top: Schematic representation of domains in PPARγ2; N-terminal A/B-domain, DNA-binding domain (DBD), hinge region, and ligand-binding domain (LBD) and indicated positions of the two mutations. Bottom: Alignment of the amino acid sequence surrounding PPARγ2 E379K and R212Q between human PPAR subtypes and PPARγ between different species. Residue positions of E379 and R212 are highlighted in green and blue, respectively. d Crystal structure of PPARγ:RXRα heterodimer bound to DNA (PPARγ in red; RXRα in gray; PDB entry 3DZY)¹¹. E379 (in green) at the end of helix 6 in PPARγ at the heterodimerization interface with RXRα DBD and R212 (in blue) in the hinge region of PPARγ are encircled. Both amino acid residues are indicated in stick format. Protein Database entry 3DZY. The figure is generated by open-source software PyMOL2 (www.pymol.org). A similar DNA-bound conformation based on SAXS was proposed by Bernardes et al.¹⁴.