Posterior Lissencephaly Associated with Subcortical Band Heterotopia Due to a Variation in the CEP85L Gene: A Case Report and Refining of the Phenotypic Spectrum

Lissencephaly describes a group of conditions characterized by the absence of normal cerebral convolutions and abnormalities of cortical development. To date, at least 20 genes have been identified as involved in the pathogenesis of this condition. Variants in CEP85L, encoding a protein involved in the regulation of neuronal migration, have been recently described as causative of lissencephaly with a posterior-prevalent involvement of the cerebral cortex and an autosomal dominant pattern of inheritance. Here, we describe a 3-year-old boy with slightly delayed psychomotor development and mild dysmorphic features, including bitemporal narrowing, protruding ears with up-lifted lobes and posterior plagiocephaly. Brain MRI at birth identified type 1 lissencephaly, prevalently in the temporo–occipito–parietal regions of both hemispheres with “double-cortex” (Dobyns’ 1–2 degree) periventricular band alterations. Whole-exome sequencing revealed a previously unreported de novo pathogenic variant in the CEP85L gene (NM_001042475.3:c.232+1del). Only 20 patients have been reported as carriers of pathogenic CEP85L variants to date. They show lissencephaly with prevalent posterior involvement, variable cognitive deficits and epilepsy. The present case report indicates the clinical variability associated with CEP85L variants that are not invariantly associated with severe phenotypes and poor outcome, and underscores the importance of including this gene in diagnostic panels for lissencephaly.

Study on the application of a new type of vertebral plate nail guide

Objective :To explore the safety and accuracy of the novel C2 laminar staple guide through in vitro experiments. Methods 40 cases of cervical spine 3D CT data were selected to produce the same two sets of 3D printed specimens (groups a and b), and the self-made guide was used to assist nail placement on group a specimens (group A: guide nail placement group), and group b Laminate nails were placed free-hand on the specimens (group B: free-hand nailing group), and a three-dimensional modeled simulated nailing was reconstructed on the computer (group C: 3D simulated nailing group). Simultaneously measure the danger level, the position of the needle exit point and the inclination angle of the screw placement position of each group. Results :In group A, 75 screws were acceptable and 5 were dangerous. The acceptable rate was 93%, and the double cortical rate was 92%. There were 62 position-acceptable screws in group B, and 18 positions were dangerous, with an acceptable rate of 77% and a double cortical rate of 32%. There was a statistically significant difference between the two groups (P <0.05). There was no significant difference in the accuracy of the needle point and the inclination angle of the nail channel between group A and group C (ideal nail channel). There was no significant difference between groups A and C (ideal nail channel). The comparison of the inclination angle of the nail channel is statistically significant (P <0.05). The results show that the screw assisted by the guide is closer to the ideal nail channel, which is safer than the manual nail placement, and can effectively improve the double cortical rate. Conclusion: The guide is universal, with stable structure, accurate guidance, and easy operation. It can be placed with bilateral lamina screws at the same time, shortening the time of nail placement, avoiding the collision of two-way cross screws, increase the rate of double cortex. Ultimately, efficiency and security can be improved.

Domain swap in the C-terminal ubiquitin-like domain of human doublecortin

Doublecortin, a microtubule-associated protein that is only produced during neurogenesis, cooperatively binds to microtubules and stimulates microtubule polymerization and cross-linking by unknown mechanisms. A domain swap is observed in the crystal structure of the C-terminal domain of doublecortin. As determined by analytical ultracentrifugation, an open conformation is also present in solution. At higher concentrations, higher-order oligomers of the domain are formed. The domain swap and additional interfaces observed in the crystal lattice can explain the formation of doublecortin tetramers or multimers, in line with the analytical ultracentrifugation data. Taken together, the domain swap offers a mechanism for the observed cooperative binding of doublecortin to microtubules. Doublecortin-induced cross-linking of microtubules can be explained by the same mechanism. The effect of several mutations leading to lissencephaly and double-cortex syndrome can be traced to the domain swap and the proposed self-association of doublecortin.