Clinical Analysis Of A Case Of Aldosterone Synthase Deficiency Caused By Novel Mutations In The CYP11B2 Gene

Background:With the continuous development and progress of medicine,in recent years,more and more attention has been paid to the research of aldosterone in maintaining homeostasis and normal physiological functions,as well as the gene,structure,regulation and clinical diseases of aldosterone synthase.Aldosterone synthase deficiency(ASD)is an extremely rare autosomal recessive genetic disease,which is caused by mutations in the aldosterone synthase(CYP11B2)gene[1].Clinical manifestations vary with age,ranging from asymptomatic growth disorders to life-threatening low blood volume and electrolyte imbalances,with severe cases occurring in infancy[2].The disease has been reported in parts of Europe,North America and the Middle East.Due to its rarity,aldosterone synthase deficiency has not been well understood,which is easy to be misdiagnosed or missed.Therefore,the prevention and treatment of aldosterone synthase deficiency should focus on early diagnosis and treatment,which is beneficial to improve the prognosis of children.With the development of molecular genetics,gene detection is helpful for the early diagnosis and timely treatment of aldosterone synthase deficiency.In the following,we will strengthen the understanding of aldosterone synthase deficiency by studying the clinical characteristics of a patient caused by novel mutations in the CYP11B2 gene.Objective:1 cases of diarrhea,vomiting,angular repeatedly with severe hyperkalemia,hyponatremia,low chlorine concentration level examination genetic metabolic disease of children clinical data were retrospectively analyzed and summarized characteristics of disease,diagnosis,process and characteristics of the CYP11B2 gene mutations,to strengthen the understanding of the disease and to make early diagnosis and prompt treatment correctly,and determine the CYP11B2 gene splicing mutation results,and the discovery of new mutations are protein function analysis.To explore the value of targeted gene detection in the diagnosis of rare endocrine and metabolic diseasesMethods:1.SubjectsA case of aldosterone synthase deficiency diagnosed in the first affiliated hospital of Zhejiang University and other family members.2.Research methods(1)Clinical data of a patient with aldosterone synthase deficiency caused by CYP11B2 gene mutation and blood tests including hormones(ACTH,17-ohp,COR,ALD,PRA)were retrospectively summarized.(2)With the consent of the medical ethics committee of the hospital,communicate with the parents and sign the informed consent letter,collect the peripheral blood of the proband and its family members,carry out the suspicious disease-causing gene testing on the proband,and verify the disease-causing gene of other family members;Genomic DNA was used to directly sequence all exons of CYP11B2.The newly discovered mutant genes were analyzed for protein function.Results:The patients appeared in infancy salt consumption,through genetic testing found for CYP11B2 gene mutation compound heterozygosity:[c.1200+1 g>A/p.L 375 CFS*1;c.448 c/1342 c>T/p.R],children with mother carried A wrong heterozygous mutations(c.448 c/1342 c>T/p.R),children with father carried A splice site mutation(1200+1g>A/c.p.L375 CFS*1),with his father and mother are carrying A hybrid mutation loci,children for compound heterozygous mutations.The mutation led to abnormal splicing,in which exon 7 and exon 8 were skipped,resulting in the deletion of exon 7 and exon 8,and the premature codon formation of exon 9 was stopped.Aldosterone synthase deficiency was confirmed by genetic testing and is a newly reported mutation.The function prediction of mutant gene protein has pathogenicity.The blood electrolyte returned to normal after the treatment with fluhydrocortisone,and the growth and development of the children gradually returned to normal after the follow-up.Conclusion:1.The child suffered from recurrent diarrhea,vomiting and wasting with severe hyperkalemia,hyponatremia and metabolic acidosis shortly after birth,which was taken as a clue to make a preliminary clinical diagnosis of aldosterone synthase deficiency,and the diagnosis was confirmed by genetic verification.2.Summarize the case characteristics and trace the disease’s idiosyncrasy clue for targeted genetic testing,which is helpful for the early diagnosis and correct and timely treatment of aldosterone synthase deficiency.In addition,genetic testing is an effective method for the diagnosis of rare endocrine and metabolic diseases.3.Two novel mutations of CYP11B2 gene were found(c.1200+1G>A/p.1375cfs*1).C.1342C>T/p 448C/),one of which is splicing mutation(c.1200+1G>A/p 1375Cfs*1),which enriched the human CYP11B2 gene mutation database.The pathogenicity of the two mutations and their effects on the tertiary structure of aldosterone synthase were predicted and analyzed.