OBJECTIVE: To detect potential variants in a family affected with Usher syndrome type I, and analyze its genotype-phenotype correlation. METHODS: Clinical data of the family was collected. Potential variants in the proband were detected by high-throughput sequencing. Suspected variants were verified by Sanger sequencing. RESULTS: The proband developed night blindness at 10 year old, in addition with bilateral cataract and retinal degeneration. Hearing loss occurred along with increase of age. High-throughput sequencing and Sanger sequencing revealed that she has carried compound heterozygous variants of the MYO7A gene, namely c.2694+2T>G and c.6028G>A. Her sister carried the same variants with similar clinical phenotypes. Her daughter was heterozygous for the c.6028G>A variant but was phenotypically normal. CONCLUSION The clinical features and genetic variants were delineated in this family with Usher syndrome type I. The results have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.
Child ; Female ; Genetic Variation ; Genotype ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Myosin VIIa ; genetics ; Night Blindness ; etiology ; Pedigree ; Phenotype ; Usher Syndromes ; genetics ; pathology

Objective:To discuss the clinical effect about the external locking compression plate(LCP) combined with lower abdominal conjoined flap for fixing the open fracture and covering the soft tissue defects on tibia.Methods:From August 2017 to December 2020, 18 patients with serve tibial open fracture were admitted into the trauma center, including 15 males and 3 females with a median age of 38 (ranged, 25-58) years old. The etiology involving: 9 cases by traffic accident, 3 by downfall, 6 by crushing, which classified as type III B( n=6) and III C( n=12) by the Anderson-Gustilo criterion. All wounds were taken radical debridement, fixed by the femur LCP and covered by the VSD during the emergency operation. The lower abdominal conjoined flap was dissected to cover the soft tissue defect, of which the dimension and pedicle length were tailored to the defect. Primary closure was performed on the donor site. Followed-up was conducted by telephone and WeChat. Results:One flap was changed to gastrocnemius myocutaneous flap because of the venous crisis. Seventeen flaps survived completely without significant complications. All the donor and recipient sites had primary healing. A mean follow-up of 15 (ranged, 12 to 18) months. The fracture healed without bone infection and bone nonunion. The aesthetic outcomes were satisfied without overgrown hairy and hyperpigmentation for all flaps. The concealed linear scar was left without hernia or other morbidity on the donor site. At the final follow-up, 12 cases were excellent and 6 cases were good evaluated by the Johner-Wruhs criteria.Conclusion:The external LCP can immobilise the knee and ankle joint with the preservation of the soft tissue, and the free lower abdominal conjoined flap was useful for covering extreme defects with concealed donor site, with enough tissue volume. The combination of both could lower the postoperative infection, reduce the operation time and shorten the hospital stay.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.