Figure 1

Pedigree of UK Family SC32 in which a putative gene mutation has been found. (A) Open circles and squares indicate unaffected individuals. Blackened circles and squares indicate affected females and males respectively. The arrow indicates family proband (SC32.1) and NGS sequenced patients are indicate by asterisks (SC32.1, SC32.16). (B) Standing posterior radiographs of proband V:3 of family SC32, showing right thoracolumbar spinal curvature in the absence of congenital vertebral abnormality. Cobb angle measurement of 40° at time of diagnosis (left panel), Cobb angle measurement of 56° before corrective surgery (middle panel), and spinal fusion (right panel). (C) Sequence obtained by Sanger sequencing of gDNA from scoliotic patient revealing the insertion of TT inducing a framshift (DE0193 lower chromatogram), compare to normal sequence of non-scoliotic patient (DE0194 upper chromatogram). (D) Representation of Human TTLL11 isoform 1 and 2 with the TTL domain showing the p.Pro524PhefsTer4 mutation (upper panel, black arrow), and partial alignment of TTLL11 by MUSCLE⁹⁶ from different species to identify conserved domains (lower panel, black arrow represents the mutated proline).