Figure 2

Figure 2 Next-generation sequencing reveals rare variants in the NOX4 gene in PAM patients.

(A) NOX4 gene structure is shown, exons are denoted as boxes, and the three rare variants found in PAM patients are marked by arrows; below, protein domains are indicated, stars show the position of the variants in the protein. (B) Sanger sequencing of the patients validated the findings from next-generation sequencing, heterozygous variants in NOX4 are shown: p.V369F, p.Y512IfsX20, and p.Y512C. Arrows highlight the nucleotide change or the start of the frameshift. (C) Patient radiographs of the hands show Pencil-in-cup deformities in metacarpophalangeal joints, osteolysis and ankylosis in proximal interphalangeal joints and destruction of the wrist (os carpale) (severe in PAM14, milder in PAM218). Feet: Severe osteolysis of the interphalangeal (IP) joints on the left side. Ankylosis of the first IP joint. The mutations found in patients are denoted NOX4^Y512IfsX20, NOX4^Y512C, and NOX4^V369F. (D) Molecular structure of NOX4. Six transmembrane domains are represented by cylinders, cytosolic domains including FAD and NADPH-binding domains are shown as boxes. e electron, FAD flavin cofactor, NADPH nicotinamide adenine dinucleotide phosphate.