Screening Of Mitochondrial Mutations And Pedigree Analysis In Patients With Early-onset And Non-obese Diabetes

Objective: To detection mitochondrial genes in patients with early-onset ande non-obese diabetes,effectively screened out the patients with mutant genes,and explored the clinical and pedigree characteristics of these patients.the purpose of this study is to provide a basis for improving the diagnosis rate of mitochondrial diabetes and giving the correct treatment plan to these patients.Methods: Collect clinical data of 83 patients with early-onset and non-obese diabetes,screen these patients for 61 known genetic mutations and screen out patients with mutations.Comparison of clinical phenotypes between patients with mutations and patients without mutations.To detection mitochondrial genes with second-generation gene sequencing in patients with clinically highly suspected mitochondrial diabetes and pedigree genetic testing for further verification.Results:(1)Screening of 61 known mutation sites in 83 patients with early-onset non-obesity diabetes using next-generation sequencing technology.A total of 42 patients(51%)carried mitochondrial mutation genes,of which 29(69%)carried T16189 C mutations.The remaining mutation sites were G3243 A,G3316A,T3394 C,T4216C,A4917 G,A12026G,A1438 G,T14783C,C16213 T,T14216C and A4833 G mutations.Compared with the group without mutant gene,the patients with mutant gene had earlier onset age,lower BMI,earlier insulin therapy,more matrilineal genetic history,lower C-peptide level and earlier occurrence of diabetic retinopathy.It can also be accompanied by hearing impairment,gastrointestinal symptoms,etc.(2)Six cases of mitochondrial diabetes patients with G3243 A mutation confirmed by genetic testing and family verification,and four of the maternal relatives of two probands carried G3243 A mutation gene,but there were no clinical symptoms.Six probands had obvious matrilineal genetic family history,earlier onset age,and earlier insulin therapy,accompanied by varying degrees of hearingabnormality,constipation and so on.Conclusion: The patients with early-onset and non-obesity diabetes,those who have been diagnosed with diabetes for a short period of time to start insulin therapy,low fasting C-peptide levels,low HOMA-IR,and have diabetic retinopathy earlier should be screened for genetic testing as soon as possible.It is recommended that patients with a high degree of suspected mitochondrial diabetes,especially with a significant maternal genetic history,be diagnosed directly by second-generation gene sequencing and screened by first-generation gene sequencing of their maternal relatives.For patients with definite mitochondrial diabetes,and the people who carry a mutated gene but have not yet shown clinical symptoms should regularly carry out multi-system clinical examinations,including relevant examinations of the heart,kidney,hearing,and ophthalmology,as well as early and correct intervention and treatment,and regular follow-up.