Adams, David R.

Sonic hedgehog signaling regulates processes of embryonic development across multiple tissues, yet factors regulating context-specific Shh signaling remain poorly understood. Exome sequencing of families with polymicrogyria (disordered cortical folding) revealed multiple individuals with biallelic deleterious variants in TMEM161B , which encodes a multi-pass transmembrane protein of unknown function. Tmem161b null mice demonstrated holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes consistent with impaired Shh signaling, but were without limb defects, suggesting a CNS-specific role of Tmem161b. Tmem161b depletion impaired the response to Smoothened activation in vitro and disrupted cortical histogenesis in vivo in both mouse and ferret models, including leading to abnormal gyration in the ferret model. Tmem161b localizes non-exclusively to the primary cilium, and scanning electron microscopy revealed shortened, dysmorphic, and ballooned ventricular zone cilia in the Tmem161b null mouse, suggesting that the Shh-related phenotypes may reflect ciliary dysfunction. Our data identify TMEM161B as a regulator of cerebral cortical gyration, as involved in primary ciliary structure, as a regulator of Shh signaling, and further implicate Shh signaling in human gyral development.

Purpose To summarise the clinical, molecular and biochemical phenotype of mannosyl-oligosaccharide glucosidase-related congenital disorders of glycosylation (MOGS-CDG), which presents with variable clinical manifestations, and to analyse which clinical biochemical assay consistently supports diagnosis in individuals with bi-allelic variants in MOGS. Methods Phenotypic characterisation was performed through an international and multicentre collaboration. Genetic testing was done by exome sequencing and targeted arrays. Biochemical assays on serum and urine were performed to delineate the biochemical signature of MOGS-CDG. Results Clinical phenotyping revealed heterogeneity in MOGS-CDG, including neurological, immunological and skeletal phenotypes. Bi-allelic variants in MOGS were identified in 12 individuals from 11 families. The severity in each organ system was variable, without definite genotype correlation. Urine oligosaccharide analysis was consistently abnormal for all affected probands, whereas other biochemical analyses such as serum transferrin analysis was not consistently abnormal. Conclusion The clinical phenotype of MOGS-CDG includes multisystemic involvement with variable severity. Molecular analysis, combined with biochemical testing, is important for diagnosis. In MOGS-CDG, urine oligosaccharide analysis via matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry can be used as a reliable biochemical test for screening and confirmation of disease.

AbstractIntroduction/AimsThe edentulous mandibular ridge and associated shallow vestibule are often seen as a challenge in the oral rehabilitation of patients. Dental implants can provide an improvement in mastication and patient satisfaction. The aim of this study is to utilize a preprosthetic mucosal flap combined with a repositional periosteal flap concomitant with an alveoloplasty and placement of endosteal implants as a single‐stage procedure in the anterior mandible. This approach provides a valued alternative for dental rehabilitation in patients with poor masticatory efficiency using a conventional denture.MethodsEight patients underwent the preprosthetic surgical plan in the oral surgery clinic of the dental school during a 1‐year period. Age, sex, preoperative, and postoperative vestibular depth, as well as hard and soft tissue elements were measured (P < .05) at 4‐6 months.ResultsMean age was 53 years ± 14.62 (N = 8). Anterior mandible height was 19 ± 4.8 mm. A significant difference was measured using a two‐tailed Student's t‐test between pre‐ and postoperative vestibular depths, respectively (3.9 mm vs 10.5 ± 0.96 mm; P < .01).ConclusionsA lip switch vestibuloplasty combined with placement of two implants provide a one‐stage procedure that is convenient, provides a shorter postoperative period, and can be financially affordable. Future research requires larger sampling to support this treatment as a standard of care.