Application Of Carrier Screening Of Monogenic Disease Based On Capillary Electrophoresis Platform

Background Through carrier screening for genetic diseases,we can effectively prevent the occurrence of certain diseases with high incidence rate in specific populations.This method is economical,accurate and reliable.It can screen out high-risk groups and reduce the risk of severe single-gene recessive genetic disease through genetic counseling and prenatal diagnosis.As a country with serious birth defects,we are facing many challenges.Many monogenic diseases can cause serious consequences of death,deformity and even disability of children.These diseases usually have no specific treatment methods,resulting in huge economic losses.Therefore,it is particularly important to screen for monogenic genetic diseases in our population.Expanded carrier screening(ECS)is receiving more and more attention in China,but its clinical application is still at the initial stage,and there are few large sample study for Chinese people.The purpose of this study is to screen the genetic variation carriers of 15 monogenic genetic diseases among the population in Anhui,Ch ina,so as to understand the genetic disease carriers of the local population and explore the application value of ECS technology in clinical practice.Objective To understand the carrying situation of pathogenic genes and common mutations in the population of Anhui Province,China,to explore the application value of ECS in clinical practice,and to provide relevant data for the construction of gene mutation datab ase belonging to the Chinese population.Methods Through the detection of ECS in 517 patients of reproductive age with normal phenotype and no family history of related genetic diseases admitted to our hospital from 2021 to 2022,410 pathogenic variants of 21 genes related to 15 diseases were detected using the first-generation sequencing analysis technology based on the capillary electrophoresis platform,and the spouses of positive carriers were tested for relevant genes,so as to evaluate the disease carrying situation of the local population,the type of genetic mutations and the frequency of couples being carrier s of the same pathogenic genes.Results Among 517 reproductive age people receiving ECS and 17 spouses receiving target gene sequencing,94 were identified as carriers of at least one disease,with a total carrier rate of 18.2%(94/517).Among them,92 cases(97.87%,92/94)were carriers of autosomal recessive diseases,1 case(1.06%,1/94)was carrier of X-linked diseases,and 1 case(1.06%,1/94)was carrier of mitochondrial genetic diseases.Of the 94 carriers,75(79.79%)carried one gene heterozygou s mutation,18(19.1 5%)carried two gene heterozygous mutations,and 1(1.06%)carried three gene heterozygous mutations.The three diseases with the highest carrying rate were hereditary deafness(6.38%,33/517),Wilson disease(3.09%,16/517)and congeni tal adrenal hyperplasia(2.51%,13/517).A total of 5 high-risk couples(3.57%,5/140)were detected in this study,of which 4 couples were carriers of the same autosomal pathogenic gene mutation,including 1 pair of GJB2-related non-syndromic deafness carriers,1 pair of alpha-thalassemia carriers and two pairs of phenylketonuria carriers,and another woman of childbearing age was a carrier of mitochondrial deafness disease.After genetic counseling,two(40%,2/5)of the couples at high risk of carrying the pathogenic gene for phenylketonuria opted for prenatal diagnosis,and amniotic fluid test showed no pathogenic variation within the specified gene range.Conclusions It is feasible and necessary to implement ECS in clinical practice.It is particularly important to screen carriers of genetic diseases before or in the early pregnancy.It can not only help clinicians provide more personalized genetic counseling to the subje cts,but also provide risk assessment and fertility guidance for high-risk families,which can effectively prevent the occurrence of monogenic diseases,thus greatly reducing the probability of birth defects.This study not only collected information about the carrying rate of each single disease gene and the genetic variation in the Chinese population,but also conducted in-depth analysis.