Study And Analysis Of A Family Of Adult Diabetes Caused By R447Q Mutation Of Glucokinase Gene

Objective Adolescent adult diabetes(maturity-onset diabetes of the young,MODY)is due to coding with β cell development and maturation of protein and enzymes associated with insulin secretion of one or several genes mutations caused by chronic hyperglycemia syndrome,autosomal dominant inheritance,is a special type of diabetes,is also the most common type of monogenic diabetes.Currently,mutations in at least 14 different genes have been shown to cause MODY isoforms 1 – 14.MODY2 caused by heterozygous mutations in the glucokinase(Glucokinase,GCK)gene is one of the most common MODY subtypes.In this study,a clinical spectrum of MODY and genetic characteristics was collected.By collecting the clinical data of all members of the family,the molecular genetic characteristics of the gene detection technology were systematically compared and analyzed,so as to clarify the causative gene,gene mutation type of the disease and the clinical phenotype of the MODY family.In order to clarify the molecular genetic mechanism of this disease,enrich the genetic database of this disease,identify the pathogenic genes of the patients in this family,and lay the theoretical foundation for the formulation of accurate and effective treatment plan.Methods This study collected a clinical phenotype and genetic characteristics in line with the characteristics of MODY Chinese non marriage family,through the proband(a 30-year-old young woman,pregnancy physical accident found increased blood sugar,no ketosis,a family history of diabetes)all exonic gene sequencing,sequencing results show that the pathogenic gene was detected in the DNA of the peripheral blood of the proband.Then,we conducted medical history collection and physical examination of 8 famous family members(including 3 diabetic patients and 5 family members without history and clinical manifestations of diabetes),obtained relevant clinical data and peripheral blood genomic DNA,and verified whether the allele was mutated by Sanger sequencing.In addition,we selected 60 healthy people as the control group,and also verified whether the gene was mutated by sanger sequencing technology.The biological function of the target gene and its expression products was predicted by the type of pathogenic gene mutations identified by whole exon gene sequencing and sanger sequencing results.Results We found a heterozygous mutation in the GCK gene of the proband with a clinical phenotype by whole-exon sequencing: c.1340G>A,p.Arg447 Gln.2.All the members of the family(including three patients with diabetes and five members without diabetes history and clinical manifestations)allele fragments for sanger sequencing,found that the family 3 generation of 9 members of four members(including three patients with diabetes and 12 year old girl with no history of diabetes)the site has the same mutation.3 Validation analysis of GCK alleles from 60 healthy individuals did not detect this mutation as a control.4.According to the relevant literature query at home and abroad,the mutation has been reported in Europe and America in the OMIM database,according to the evidence.Thus,this mutation was first identified in an Asian population.Conclusion The pathogenic gene and its mutation type in diabetes patients within one MODY 2 family were identified,and the mutation was found to be the first reported in Asia.We summarized the clinical phenotype of the patients in the family and recorded the results of the glucose metabolism test.These data filled the genetic and clinical database of MODY 2 in China and even in Asia,further enriched the database of GCK gene mutations at home and abroad,and were expected to clarify the molecular consequences of GCK gene mutations in MODY 2,and laid for the continuous identification and study of different mutations of GCK gene in the future.Moreover,the mechanisms involved with the mutation at this site still require cell-level functional experiments.