Figure 1
From: SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts
A Radiographs of subjects with the Västerbotten form of intermediate osteopetrosis, and sequencing of the SNX10 gene. (A–D) Skeletal radiographs of a girl at the age of three years (Pt9), showing characteristic features of intermediate osteopetrosis. (A) Skull: Increased bone density of the skull base, frontal bossing and VP-shunt (B) AP view of the legs: “Erlenmeyer flask” shape of the femoral diaphysis. Longitudinal and transverse bands of lesser density in the metaphyses. Bone-within-bone pattern in the epiphyses in the knee. (C) Lateral view of the spine: Very dens endplates of the vertebral bodies, so called “sandwich vertebrae”. The ribs (seen in part) are broad and dens. (D) AP view of the left arm: No fractures or sign of rickets, “bone-within-bone” pattern of the phalanges. (E,F) Magnetic resonance imaging of the brain, and spine in an 11-year-old boy. MRI shows cerebellar tonsillar descent through the foramen magnum, a foramen magnum narrowing, and signs of brain stem compression with resulting syringo-hydromyelia. (G,H) Consequence of the c.212 + 1 G > T variant on (G) genomic level and (H) transcript level. (G) Sequencing of DNA from a control (top), a heterozygous carrier (middle) and a homozygous patient (bottom) for the c.212 + 1 G > T variant. The variant changes the donor splice site at the 5′ end of intron 4 from GT to TT. This leads to a predicted use of an alternative donor splice site 16 nucleotides upstream of intron 4. (H) Sequencing of cDNA from a control (top) and a patient (bottom) confirms the use of an alternative splice site and the skipping of 16 bp leading to a frame shift and a premature stop codon (p.S66Nfs * 15) at the protein level.
