Study Of Glycometabolistic Abnormalities Caused By Monogenic Mutations

Objective:To identify the related genes for glycometabolistic abnormalities caused by monogenic mutations in Chinese population,to study the etiopathogenisis at the gene-molecular biological level.We can devide the cases into seven catagories at this level:hyperglycemia and hypoglycemia caused by KCNJ11,ABCC8 mutations;hyperglycemia and hypoglycemia caused by HNF1A,HNF4A mutations;hyperglycemia and hypoglycemia caused by GCK mutations; hypoglycemia caused by GLUD1 mutations;hypoglycemia caused by HAD1 mutations;hyperglycemia caused by ISN mutations;diabetes mellitus with extrapancreatic features caused by NEUROD1, KLF11, CEL.HNF1B,PAX4 and mitochondrial gene et al. mutations.The special treatments would be carried on to the genetic diagnosed patients.Methods:1. Collected clinical datas of 20 patients and their pedigrees(at least parents) who are seriously considered to be suffering glycometabolistic abnormalities caused by monogenic mutations. After getting informed consent from them, peripheral venous blood were drawn for genome DNA extraction.Exons of gene KCNJ11, ABCC8, HNF1A, HNF4A, PAX4, GCK, GLUD1, HAD1, ISN, NEUROD1, HNF1B, KLF11, CEL and mitochondrial gene(including 5',3'untranslated regions) were chosen to amplify by polymerase chain reaction for direct sequencing according to their special clinical characteristics. The functional studies for new founded mutations are followed.2. According to the results of gene sequence, special treatments were given to the patients under a strict glucose level monitoring. Detected blood Results:1. Genic variances of 11 out of 20 pedigrees were identified:KCNJ11 was the related gene for 2 pedigrees; ABCC8 was the related gene for 4 pedigrees; HNF1A was the related gene for 1 pedigree; GLUD1 was the related gene for 2 pedigrees; GCK was the related gene for 2 pedigrees.These variances were not found in 50 normal contrasts.Some of them were identified to be the mutations,the followed functional studies for the other variances were necessary.2. The special treatment according to the genetic categories did well in the patients,the blood glucose levels were stable,other clinical indications were ameliorated There were no drug side effects.Conclusions:This is the first study of glycometabolistic abnormalities caused by monogenic mutations in Chinese population.Discussed the etiopathogenisis at the gene-molecular biological level,the special clinical characteristics and the treatment for each genetic category.It has value on acknowledging the progress of the disease, genetic screening and special treatment.