Kinesin motors play a fundamental role in development by controlling intracellular transport, spindle assembly, and microtubule organization. In humans, patients carrying mutations in KIF11 suffer from an autosomal dominant inheritable disease called microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR). While mitotic functions of KIF11 proteins have been well documented in centrosome separation and spindle assembly, cellular mechanisms underlying KIF11 dysfunction and MCLMR remain unclear. In this study, we generate KIF11-inhibition chick and zebrafish models and find that KIF11 inhibition results in microcephaly, chorioretinopathy, and severe developmental defects in vivo. Notably, loss-of-function of KIF11 causes the formation of monopolar spindle and chromosome misalignment, which finally contribute to cell cycle arrest, chromosome instability, and cell death. Our results demonstrate that KIF11 is crucial for spindle assembly, chromosome alignment, and cell cycle progression of progenitor stem cells, indicating a potential link between polyploidy and MCLMR. Our data have revealed that KIF11 inhibition cause microcephaly, chorioretinopathy, and development disorders through the formation of monopolar spindle, polyploid, and cell cycle arrest.

OBJECTIVE: Oliver-McFarlane syndrome (OMCS) is an autosomal recessive inherited disease resulting from PNPLA6 mutations that results in intellectual impairment and profound short stature. To obtain a better understanding of the genotype-phenotype correlations for PNPLA6-related disorders, we reported the 14th OMCS case and summarized all the reported cases of OMCS.
METHODS: We collected clinical biochemical and data and brain MRI data and used whole-exon gene detection and analysis tools to evaluate the pathogenicity of the variants, including PolyPhen-2 and Mutation Taster, and we also generated three-dimensional protein structures and visualized the effects of altered residues with I-TASSER and PyMOL Viewer software.
RESULTS: The patient presented with trichomegaly and multiple pituitary hormone deficiencies. Brain MRI showed small pituitary and bilateral paraventricular leukomalacia. Novel variants (c.1491G > T and c.3367G > A) in the PNPLA6 gene were detected in the proband and verified by direct sequencing. Amino acid residues of Gln497 and Gly1123 are predicted to be damaging and destroy the three-dimensional protein structures of the protein. In follow-up, this patient could neither walk nor hold his head erect and had not spoken one word at the age of one year and ten months. Moreover, there is no obvious hot spot mutation in any of the reported allelic variants. Interestingly, the majority of mutations are located in the phospholipid esterase domain, which is responsible for esterase activity.
CONCLUSIONS: We identified two novel variants of the PNPLA6 gene in an OMCS patient, which will help to better understand the function of PNPLA6 and genotype-phenotype correlations for PNPLA6-related disorders.

Background Central serous chorioretinopathy (CSC) is a widespread retinal disorder, and 30-50% of patients eventually result in retinal pigment epithelium atrophy and irreversible vision loss. Aim of the review To evaluate the effectiveness of medications based on anti-vascular endothelial growth factor (anti-VEGF) on central serous chorioretinopathy (CSC). Method A systematic search on anti-VEGF medication treatments for CSC was performed in Pubmed, Embase, and the Cochrane Library prior to May 2016. The main outcome variables were best-corrected visual acuity (BCVA) and central macular thickness (CMT). All effects were analyzed via Review Manager 5.3. Results Fourteen studies were incorporated with a total of 266 eyes, divided into a comparative group and a non-comparative group. The comparative group included acute and chronic CSC studies, while the non-comparative group included chronic CSC only. Meta-analysis revealed that for acute CSC, anti-VEGF treatment was not superior to observation at a 6-month follow-up in BCVA and CMT. For chronic CSC in the comparative group, no significant difference was observed between anti-VEGF treatment and observation in BCVA; however, the observed difference in CMT (WMD = -67.78, 95% CI 20.17-115.38) was statistically significant. In the non-comparative group, significant differences were observed after anti-VEGF treatment in BCVA and CMT at 1, 6, and 12 months follow-ups. Conclusion Our meta-analysis partially indicated that anti-VEGF medications might be a viable choice for the treatment of chronic CSC; however, due to the self-limiting nature of CSC, care should be applied in the clinical application of anti-VEGF medications.