EFL1 variants in SBDS⁻ SDS patients. (A) Noncontrast T1-weighted abdominal magnetic resonance (I-1) or computed tomography images (II-1 and III-1) showing a diffuse enlargement with lipomatosis of the pancreas (arrows; upper) and both knees with metaphyseal widening and irregularities in the femora in the 3 patients and associated genu varum in III-1 (lower). (B-D) Pedigrees and Sanger sequencing traces showing the inherited EFL1 variants and the de novo SBDS^p.Asp110Asn variant in the 3 families. DNA was extracted from whole-blood samples. Note that the lower-case nucleotide letters were used on top of the Sanger traces to reflect their minor allelic representation in the patient samples. (E) The residues with nonsynonymous changes in EFL1 and SBDS are evolutionarily conserved. The arrowheads on the protein maps denote previously reported pathogenic variants (blue, missense; red, loss of function). (F) Molecular modeling–based structural analysis using PDB 5ANC.⁷ The insets show the detailed interactions involving EFL1 His30, Thr1069, and SBDS Asp110. B.t., Bos taurus; C.i., Ciona intestinalis; D.r., Danio rerio; G.g., Gallus gallus; H.s., Homo sapiens; M.m., Mus musculus; O.c., Oryctolagus cuniculus.