A novel SOX10 mutation causing Waardenburg syndrome type 2 by expressing a truncated and dysfunctional protein in a Chinese child.

OBJECTIVES: This study aimed to identify the causative variants in a patient with Waardenburg syndrome (WS) type 2 using whole exome sequencing (WES). METHODS: The clinical features of the patient were collected. WES was performed on the patient and his parents to screen causative genetic variants and Sanger sequencing was performed to validate the candidate mutation. The AlphaFold2 software was used to predict the changes in the 3D structure of the mutant protein. Western blotting and immunocytochemistry were used to determine the SOX10 mutant in vitro. RESULTS: A de novo variant of SOX10 gene, NM_006941.4: c.707_714del (p. H236Pfs*42), was identified, and it was predicted to disrupt the wild-type DIM/HMG conformation in SOX10. In-vitro analysis showed an increased level of expression of the mutant compared to the wild-type. CONCLUSIONS: Our findings helped to understand the genotype-phenotype association in WS2 cases with SOX10 mutations.

Dexmedetomidine Attenuates Renal and Myocardial Ischemia/Reperfusion Injury in a Dose-Dependent Manner by Inhibiting Inflammatory Response.

OBJECTIVE: To investigate the effect of dexmedetomidine (DEX) against renal and myocardial ischemia/reperfusion (I/R) injury induced by renal I/R and explore its potential mechanism. METHODS: Male Wistar rats were randomly allocated to sham, I/R, D1, D2 and D3 group. The sham group received laparotomy without a renal ischemia. I/R injury model was induced by bilateral renal pedicle clamping for 120 min followed by 3 h of reperfusion in I/R, D1, D2 and D3 group. Then D1, D2 and D3 group received DEX of 25 µg/kg, 50 µg/kg and 100 µg/kg by intraperitoneal injection at 30 min from ischemia onset, respectively, and I/R group received normal saline. Renal histopathology, myocardial histopathology and inflammatory cytokines were assessed. RESULTS: Renal and myocardial tissues were normal in the sham group. Pathological damage showed a trend of I/R>D1>D2>D3 group in renal and myocardial tissue, and the damage was negatively correlated with the dose of DEX. The concentration of creatinine and blood urea nitrogen in serum showed a trend of I/R>D1>D2>D3>sham group. The concentration of tumor necrosis factor α in renal and myocardial tissue showed a trend of I/R>D1>D2>D3>sham group. The concentration of interleukin-10 in renal and myocardial tissue showed a trend of D3>D2>D1>I/R>sham group. CONCLUSION: DEX could attenuate renal and myocardial I/R injury induced by renal I/R in a dose-dependent manner, at least in part, through its inhibitory effects on inflammatory response.