Fig. 1

Clinical features of families and segregation of identified variants. A. Family pedigree of ZFD-01. Filled symbols indicate the affected individuals. Double lines depict consanguinity. An asterisk (*) indicates the individual for whom whole genome sequencing was performed. Genotypes are provided for the individuals whose samples were collected. B. Family pedigree of ZFD-02. C. An affected individual IV:3 from family ZFD-01: proportionate short stature is evident. D. Lateral view of his spine radiograph shows severe platyspondyly (arrow) and metaphyseal cupping at distal ribs (arrowhead). E. Lower limb radiograph shows slightly abnormal metaphyseal shaping (overtubulation) of the distal femurs, thin fibulae (arrow) and mild valgus deformity with laterally placed patellae (arrowhead). F. Radiograph of the hands of IV:3 of ZFD-01 revealed short metacarpals and abnormality in the shape of the carpal structures. G. An affected individual IV:11 from family ZFD-02. H. His legs showing vagus deformity I. hands are normal while J. the older individuals show signs of arthropathy. K. Hand radiographs show normal structures, including normal carpal bones (arrowhead) in the youngest subject L. older subject shows significant loss of articular cartilage in the digits and the wrist, together with erosion of the carpal bones. M. Radiographs of the lower limbs of the boy (IV:11 of ZFD-02) show gracile bones and severe valgus deformity N. The spine radiograph in the boy (left) shows normal vertebral heights but severe platysplondyly in the older individual (right). O. Partial chromatograms of PCNT sequence P. Partial chromatograms of DNA sequence of RAB33B. The red arrow indicates the deleted nucleotide. Q. A visual representation of RAB33B protein, red arrow indicates the frameshift variant