Analysis of an adult diabetes mellitus caused by a rare mutation of the gene:A case report

BACKGROUND This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence,featuring a unique mutation in the peroxisome proliferator-activated receptor gamma(PPARG)gene.Data Access Statement:Research data supporting this publication are available from the NN repository at www.NNN.org/download/.CASE SUMMARY The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family members.Additionally,high-throughput sequencing was conducted to analyze the PPARG genes of the patient,her siblings,and their offspring.The results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy,accompanied by insulin resistance and hypertriglyceridemia.Furthermore,these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation patterns.The results from the gene detection process demonstrated a heterozygous mutation of guanine(G)at position 284 in the coding region of exon 2 of PPARG,which replaced the base adenine(A)(exon2c.284A>Gp.Tyr95Cys).This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated protein.Notably,both of her siblings harbored a nucleotide heterozygous variation at the same site,and both were diagnosed with diabetes.CONCLUSION The PPARG gene mutation,particularly the p.Tyr95Cys mutation,may represent a newly identified subtype of maturity-onset diabetes of the young.This subtype is characterized by insulin resistance and lipid metabolism disorders.

Tescalcin is an unfavorable prognosis factor that regulats cell proliferation and survival in hepatocellular carcinoma patients

Background:Hepatocellular carcinoma(HCC)is a major health problem and a primary cause of cancer-related death worldwide.Although great advances have achieved recently by large-scale high-throughput analysis,the precise molecular mechanism underlying HCC progression remains to be clearly elucidated.We investigated the relationship between Tescalcin(TESC),a candidate oncogene,and clinicopathological features of HCC patients and explored the role of TECS in HCC development.Methods:To identify new genes involved in HCC development,we analyzed The Cancer Genome Atlas liver cancer database,and TESC was selected for further investigation.HCC tissue microarray analysis for TESC and its association with clinicopathological features were performed to investigate its clinical significance.TESC was knocked down by using short-hairpin RNAs.Cell proliferation was analyzed by WST-1 assay and cell counting.Cell apoptosis was tested by fluorescence-activated cell sorting.A subcutaneous xenograft tumor model in nude mice was established to determine the in vivo function of TESC.Affymetrix microarray was used to identify its molecular mechanism.Results:TESC was significantly increased in HCC tissues compared with the adjacent normal liver tissues.High expression of TESC was detected in 61 of 172 HCC patients by tissue microarray.Large tumor(>5 cm)and elevated total bilirubin were associated with high TESC expression(both P<0.050).In multivariate analysis,TESC was identified as an independent prognostic factor for short overall survival of HCC patients.TESC knockdown impaired HCC cell growth in vitro and in vivo.TESC knockdown significantly increased cell apoptosis in HCC cell lines.Furthermore,Affymetrix microarray analysis revealed that TESC knockdown inhibited tumor proliferation-related pathways while activated cell death-related pathways.Conclusion:TESC was identified as an independent prognostic factor for short overall survival of HCC patients,and was critical for HCC cell proliferation and survival.