Fig. 1

Identification of a KIAA0556 nonsense mutation in a family with JBTS. a Pedigree of the multiplex consanguineous family with JBTS. The index (boxed in red) was submitted for exome capture, and the individuals denoted with asterisks were available for segregation testing. MRI cuts from patient 1 indicate ectopic posterior pituitary with severe hypoplasia/aplasia of anterior pituitary; vermis hypoplasia; superior cerebellar peduncle horizontal and thick with slightly deep interpeduncular fossa and enlarged prepontine cistern with increased vertical orientation of the brain stem. Patient 2 MRI reveals mild vermis hypoplasia; superior cerebellar peduncle horizontal; slightly deep interpeduncular fossa, and normal pituitary. MRI of patient 3 shows ectopic posterior pituitary with severe hypoplasia/aplasia of anterior pituitary; vermis hypoplasia; superior cerebellar peduncle horizontal and thick with dysmorphic mesencephalon; asymmetric cerebellar peduncle with flattened interpeduncular fossa and enlarged prepontine cistern with increased vertical orientation of the brain stem. b Filtering scheme of the exomic variants effectively narrowed the list of candidates to a single variant, KIAA0556:c.2674C > T:p.Q892*, the sequence chromatogram of which is shown in (c). d RT-PCR reveals near absence of the KIAA0556 transcript in patient cells compared with control