Analysis On Clinical Phenotypes And Genotypes Of 22 Patients With Congenital Absence Of The Vas Deferens

Objective:To describe the clinical phenotypes and mutations of CFTR gene in Chinese patients with congenital absence of the vas deferens(CAVD),to investigate the correlation and mutation of ADGRG2,SLC9A3,SCNN1B and CA12 genes with the risk of CAVD,and to establish a diagnosis and treatment process suitable for the Chinese CAVD population.Methods:1.The clinical data of 22 isolated CAVD patients were analyzed and evaluated,and the fertility was followed up.2.All exons and flanking sequences and 1.4kb sequence in front of promoter and(TAAA)n short tandem repeat were detected by PCR and Sanger sequencing.3.2 pedigrees were collected for genetic analysis to evaluate the genetic risk of the offspring.4.ADGRG2,SLC9A3,SCNN1B CA12 and other CAVD susceptibility genes were identified by next-generation sequencing technology,and the results were verified by Sanger sequencing.5.Use bioinformatics software to analyze the harmfulness of novel mutations.Results:1.Most of the 22 CAVD patients had normal testis and epididymis,and a few cases may loss the corpus and cauda of epididymis;the patients had a low ejaculation,severe oligospermia or azoospermia;increased semen acidity and decreased concentration of fructose and neutral α-glucosidase but a normal level of sexual hormones;During the follow-up period(up to 1 February 2021),15 healthy live babies were born;2.A total of 16 variants of CFTR gene were detected in 22 patients.Among them,p.L136R was novel,and the frequencies of 5T,TG12-5T and TG13-5T are 25%,15.9%and 9.1%,respectively.3.The pathogenic mutations in the 2 pedigrees were p.R553X and TG13-5T,respectively.4.All patients underwent next-generation sequencing and found 1 ADGRG2 missense mutation,3 SLC9A3 missense mutations,2 SCNN1B and 1 CA12 missense mutations.Among them,p.V1651 in the SLC9A3 gene was firstly reported in CAVD patients.Conclusion:This study summarized the clinical characteristics of Chinese CAVD patients,described the distribution of CFTR gene mutations and polymorphisms,and reported a novel mutation(p.L136R);Also we had identified the genetic causes of the 2 CAVD families and reported the results of assisted reproduction,emphasized the importance of genetic counseling;finally,we preliminarily described the mutation spectrum of ADGRG2,SLC9A3,SCNN1B and CA12 genes in CAVD patients,and put forward our recommendations for the diagnosis and genetic counseling of Chinese CAVD patients.