Figure 1.

The craniofacial features of a newly identified CLSD patient at 21 month (A, B, and C) are very similar to those of known CLSD patients (D, E, and F) (2, 3). They have high and prominent forehead, with increased vascular marking in the area of the open anterior fontanel, similar shape of the eyebrows, obvious hypertelorism (the center of the pupil is marked by asterisk) and similar shape of the nose with wide and prominent nasal bridge and anteverted nares. The philtrum is long and the mouth is large and with thin upper lip in both cases. Lateral skull x-rays document large and hypomineralized calvaria in the area of the anterior fontanel (C and F). (G) Illustration of the c.2104A>G mutation (ATG>GTG, M702V). (H) Sequence alignment of SEC23. Invariant residues are shown in red. The human M702 residue shown in green is conserved in higher eukaryotes and corresponds to the yeast L708 residue shown in green. A and B after the name of indicated species represent SEC23A and SEC23B, respectively. (I) X-ray crytallographic model of a yeast Sec31 fragment (cyan) in complex with yeast Sar1p (red) and yeast Sec23p (orange) (10), with Sec24p (light green) included based on the structure of the Sar1p-Sec23p-Sec24p complex modified from the previous report (17). Because human F382 (yeast F380) is buried under the surface of the structure, two residues adjacent to F302 were colored blue and labeled “F382L”. The positions of the yeast residues corresponding to human M702 and P703 are colored yellow and labeled “M702V”. (J) Secretion defect of procollagen in M702V cells was shown by using immunoblotting. Ribophorin 1 and β-actin were also probed as loading controls.