Identification of Maturity-Onset Diabetes of the Young Caused by Mutation in FOXM1 via Whole-Exome Sequencing in Northern China.

Diabetes mellitus is a highly heterogeneous disorder encompassing different types with particular clinical manifestations, while maturity-onset diabetes of the young (MODY) is an early-onset monogenenic diabetes. Most genetic predisposition of MODY has been identified in European and American populations. A large number of Chinese individuals are misdiagnosed due to defects of unknown genes. In this study, we analyzed the genetic and clinical characteristics of the Northern China. A total of 200 diabetic patients, including 10 suspected MODY subjects, were enrolled, and the mutational analysis of monogenic genes was performed by whole-exome sequencing and confirmed by familial information and Sanger sequencing. We found that clinical features and genetic characteristics have varied widely between MODY and other diabetic subjects in Northern China. FOXM1, a key molecule in the proliferation of pancreatic ß-cells, has a rare mutation rs535471991, which leads to instability within the phosphorylated domain that impairs its function. Our findings indicate that FOXM1 may play a critical role in MODY, which could reduce the misdiagnose rate and provide promising therapy for MODY patients.

[Changes of protein kinase C activity in experimental presyrinx state in rabbits].

OBJECTIVE: To investigate the changes of protein kinase C (PKC) activity and its role in the development of presyrinx state in rabbits. METHODS: Presyrinx state was established in 56 rabbits by intra-cisternal injection of kaolin. At 1, 3, 7, 14, and 21 days after the injection, the water content in the upper cervical spinal cord was measured, its pathological changes observed microscopically and the PKC activity determined with substrate phosphorolysis kinase assay. RESULTS: Spinal cord edema occurred in rabbits one day after kaolin injection, with water content of (68.35-/+0.70)%, which increased to (72.70-/+0.88)% on day 3, reaching the peak level of (72.92-/+0.86)% on day 7, followed by gradual decline after 3 weeks [(70.03-/+0.77)%]. The membrane PKC activity increased from 5.67-/+0.26 pmol.mg(-1).min(-1) on day 1 after the injection to reach the peak level on day 7 (13.27-/+3.15 pmol.mg(-1).min(-1)), which was maintained till day 14 with subsequent decrease to 8.85-/+1.56 pmol.mg(-1).min(-1) on day 21. The cytoplasmic PKC activity showed changes of a reverse pattern. CONCLUSION: In rabbits with experimental presyrinx state, PKC translocation and activation is involved in ischemic spinal edema.