Mutations in C1orf194, encoding a calcium regulator, cause dominant Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy exhibiting great clinical and genetic heterogeneity. Here, the identification of two heterozygous missense mutations in the C1orf194 gene at 1p21.2-p13.2 with Charcot-Marie-Tooth disease are reported. Specifically, the p.I122N mutation was the cause of an intermediate form of Charcot-Marie-Tooth disease, and the p.K28I missense mutation predominately led to the demyelinating form. Functional studies demonstrated that the p.K28I variant significantly reduced expression of the protein, but the p.I122N variant increased. In addition, the p.I122N mutant protein exhibited the aggregation in neuroblastoma cell lines and the patient's peroneal nerve. Either gain-of-function or partial loss-of-function mutations to C1ORF194 can specify different causal mechanisms responsible for Charcot-Marie-Tooth disease with a wide range of clinical severity. Moreover, a knock-in mouse model confirmed that the C1orf194 missense mutation p.I121N led to impairments in motor and neuromuscular functions, and aberrant myelination and axonal phenotypes. The loss of normal C1ORF194 protein altered intracellular Ca2+ homeostasis and upregulated Ca2+ handling regulatory proteins. These findings describe a novel protein with vital functions in peripheral nervous systems and broaden the causes of Charcot-Marie-Tooth disease, which open new avenues for the diagnosis and treatment of related neuropathies.

Applied anatomy of a new approach of endoscopic technique in thyroid gland surgery.

OBJECTIVE: To explore the feasibility and safety of transtracheal assisted sublingual approach to totally endoscopic thyroidectomy by studying the anatomical approach and adjacent structures. METHODS: A total of 5 embalmed adult cadavers from Chengdu Medical College were dissected layer by layer in the cervical region, pharyngeal region, and mandible region, according to transtracheal assisted sublingual approach that was verified from the anatomical approach and planes. A total of 15 embalmed adult cadavers were dissected by arterial vascular casting technique, imaging scanning technique, and thin layer cryotomy. Then the vessel and anatomical structures of thyroid surgical region were analyzed qualitatively and quantitatively. Three-dimensional visualization of larynx artery was reconstructed by Autodesk 3ds Max 2010(32). Transtracheal assisted sublingual approach for totally endoscopic thyroidectomy was simulated on 5 embalmed adult cadavers. RESULTS: The sublingual observed access was located in the middle of sublingual region. The geniohyoid muscle, mylohyoid seam, and submental triangle were divided in turn in the middle to reach the plane under the plastima muscles. Superficial cervical fascia, anterior body of hyoid bone, and infrahyoid muscles were passed in sequence to reach thyroid gland surgical region. The transtracheal operational access was placed from the cavitas oris propria, isthmus faucium, subepiglottic region, laryngeal pharynx, and intermediate laryngeal cavit, and then passed from the top down in order to reach pars cervicalis tracheae where a sagittal incision was made in the anterior wall of cartilagines tracheales to reach a ascertained surgical region. CONCLUSION: Transtracheal assisted sublingual approach to totally endoscopic thyroidectomy is anatomically feasible and safe and can be useful in thyroid gland surgery.