A Rare Case Of The AVPR2 Gene Mutation Caused Congenital Nephrogenic Diabetes Insipidus With Intracranial Calcification And Literature Review

Objective To provide evidence for clinical diagnosis and treatment,we retrospectively analyzed the clinical data,diagnosis,and treatment process of an intracranial calcification(ICC)patient with intermittent headache,polydipsia,and polyuria,and we summarized the clinical characteristics of intracranial calcification from literature.Methods We collected and analyzed the patient’s data,including gender,age,onset time,current medical history,history,physical examination,laboratory test results,and imaging examination results.After filing by the hospital ethics committee and obtaining the informed consent of the patient and family members,5ml of venous blood from the proband and his parents was collected using EDTA anticoagulation tubes and stored at-20°C.Using the genomic DNA derived from the blood of the subject as the test material,the second-generation DNA sequencing technology was performed to detect the mutation site in the exon region,the site was verified by sanger,and the mutation site was evaluated for the pathogenicity of genetic variation.Through the Human Gene Mutation Database(HGMD)and the Online Mendelian Inheritance in Man(OMIM)database,the gene structure,biochemical characteristics,molecular genetics,mutation type,and disease phenotype of the gene can be obtained.Using "Congenital Nephrogenic Diabetes Insipidus ","Hereditary Nephrogenic Diabetes Insipidus " and "AVPR2" as keywords,we searched Pub Med,Chinese National Knowledge Infrastructure(CNKI),Wanfang database,and VIP database to find the domestic literature about AVPR2 gene mutation,recorded mutation site and mutation mode of each reported cases.Using "Nephrogenic Diabetes Insipidus "," Intracranial Calcification " as keywords,we searched Pub Med,Embase,The Cochrane Library,Chinese National Knowledge Infrastructure(CNKI),Wanfang database,and VIP database to screen out the patients who diagnosed nephrogenic diabetes insipidus and intracranial calcification,and the general information,clinical symptoms,imaging data and treatment of these patients were collected.Results The main clinical manifestations of the patient were headache,polyuria and polydipsia.Central diabetes insipidus was excluded and he was diagnosed with nephrogenic diabetes insipidus.Genomic DNA sequencing of the coding regions of the arginine vasopressin receptor type 2(AVPR2)gene in the proband and his parents was performed.A heterozygous mutation p.L83 Q in C.248 T > A gene was verified by DNA sequencing.His mother,as an asymptomatic carrier,had the same heterozygous mutation.The gene of his father is normal.The C.248 T > A is the first AVPR2 gene mutation reported in China.The paper analyzed the causes and characteristics of 25 reported nephrogenic diabetes insipidus cases with intracranial calcification and discussed the relationship between nephrogenic diabetes insipidus,intracranial calcification,headache,convulsion,and mental retardation.Conclusion 1.This is the first case of CNDI with X-linked recessive inheritance characterized by L83 Q mutation reported in China.2.CNDI is a rare cause of ICC.Early diagnosis and timely treatment can delay the progress of the disease.