Prenatal Diagnosis And Genetic Analysis Of Facioscapulohumerial Muscular Dystrophy Type 1

Background and objectiveFacioscapulohumerial muscular dystrophy(FSHD)is an autosomal dominant genetic disease,which is the third hereditary neuromuscular disease,with an incidence of 1/10000-1/20000.Currently,there is no effective treatment.Karyomapping technology is currently commonly used for Pre-implantation Genetic Diagnosis(PGD).It is a genome-wide Genetic disease analysis method that can detect whether the fetus carries the haplotype fragment to determine whether it has disease.Bio nano single molecule optical mapping technology can determine the rearrangement,inversion and other genomic information of large fragments of DNA by single strand fluorescence labeling,imaging and data analysis of super-long fragments of DNA.At present,the length of DNA fragment detected by Bionano single-molecule optical map can completely cover the pathogenic fragment of FSHD1,which can be used for FSHD1 gene detection.In this study,Bionano technology and Karyomapping technology were used simultaneously to conduct prenatal diagnosis of FSHD1 patients' families,so as to clarify the feasibility of the two methods in the prenatal diagnosis of FSHD1,and to test the accuracy of the two methods in the prenatal diagnosis ofFSHD1 through mutual verification of the two methods.Methods1.This study selected 12 families of patients with facial-acromiohumeral muscular dystrophy type 1 who had been diagnosed with clinical and genetic diagnosis at the genetics and prenatal diagnosis center of the first affiliated hospital of zhengzhou university from January 2018 to December 2019,and recorded their clinical characteristics,genetic diagnosis results and family history in detail.2.Bionano single molecule optical mapping technique was used for molecular diagnosis of the progenitor in the family,and the number of D4Z4 repeats and the allele 4qA/B of FSHD1 patients were determined.3.The Karyomapping technology was used for prenatal diagnosis of FSHD1 fimilies with family history.4.Bionano monomolecular optical mapping technology was used for molecular diagnosis of fetal samples,and the detection results were compared with those of Karyomap gene chip for follow-up.Results1.The Bionano single molecule optical mapping technique was used to verify the molecular diagnosis of 12 progenies of FSHDl family,and the results showed that the number of D4Z4 sequence repeats in patients ranged from 2 to 5,all of which were 4qA alleles.2.The Karyomapping technology was used to make 14 prenatal diagnoses in the 12 families,and the results showed that the fetuses were patients for 7 times and the fetuses were normal for 7 times.3.Bionano single-molecule optical mapping technique was applied to the genetic diagnosis of fetus,and the results were consistent with those obtained by Karyomap gene chip technique.ConclusionsThis study applies Karyomap gene chip technotogy in combination with Bionano single molecule optical mapping technology to FSHD1 family make prenatal diagnosis patients,the comprehensive application of the two methods of relative to the traditional Southern Blot detection,greatly shorten the testing time,improve the detection speed,and increases the detection accuracy,less,but because the test sample still need large sample further validated.