FIGURE 1

FIGURE 1

Identification of homozygous SMC5 in‐frame deletion in the patient with primordial dwarfism and severe insulin resistance. (A–F) Clinical features in the patient included proportionate short stature (A) and severe acanthosis nigricans in the antecubital fossae (B and C), axillae (D and E) and back of the neck (F), along with skin tags. (G) Pedigree diagram of the consanguineous family. (H) Representative Sanger sequencing of the nonsense allele in the sister, the heterozygous allele in parents and the homozygous allele in patients. (I) Position of the p.Arg372del variant located in the binding domain of SMC5 (grey, p. 302–373) with the NSMCE2 protein. A multispecies alignment is shown to highlight the strong conservation of the deleted amino acid, p.Arg372 (red asterisk). Black arrows indicate SMC5 residues important for binding with NSMCE2, as described.²⁹