To Evaluate The Value Of IMPATT Method In The Diagnosis Of Marfan Syndrome

Objective:Marfan syndrome is an autosomal dominant systemic connective tissue disease.The purpose of this study was to preliminarily understand the accuracy and efficiency of the IMPATT method detection kit in the diagnosis of MFS in practical clinical work,and to test the consistency with the gold standard in the diagnosis of MFS.It provides a new idea for the rapid,accurate,convenient and low-cost diagnosis of MFS in future clinical work.Methods:Our research group has previously studied the application of IMPATT method in the actual clinical diagnosis of MFS,which is a method based on high-throughput sequencing technology to detect Marfan and syndrome-like related mutations.In this study,the 2010 revised Ghent II criteria were used as the gold standard for diagnosing MFS.According to the sample size calculation,referring to the inclusion and exclusion criteria,a total of 147 subjects who were treated The First Affiliated Hospital of Gannan Medical University were included.According to the relevant information and relevant clinical indicators in "Diagnostic Steps and Specific Forms of Marfan Syndrome"(see Appendix 1)and "Clinical Research Index Card for Evaluating the Value of IMPATT Method in the Diagnosis of Marfan Syndrome"(see Appendix 2)Objective and detailed records.Used modem technique of absorption modem technique of absorption modem technique of absorption modem technique of absorption modem technique of absorption modem technique of absorption modem.For each participant,a disposable vacuum negative pressure EDTA-K2(ethylenediamine tetraacetic acid)purple anticoagulant blood collection tube was used to collect a portion of 5ml of fasting fresh peripheral venous blood,and the collected blood samples were extracted and qualified DNA samples were sent out Go to Shenzhen Ruiao Kangchen Biotechnology Limited Company for high-throughput sequencing with the IMPATT method.The IMPATT method kit covers8 related genes of MFS and similar syndromes: FBN1,FBN2,TGFBR1,TGFBR2,TGFB2,TGFB3,SKI,SMAD3.Sequencing results were analyzed according to the relevant guidelines of the American College of Medical Genetics and Genomics.After the sequencing is completed,the personal information and diagnosis results of the included participants will be desensitized,and the random number table method will be used for the data number and grouping of the participants,and the extraction and grouping of clinical diagnosticians(with the title of deputy chief physician and above)Using random number table method.All participants were diagnosed with the following four different diagnostic methods:(1)Single department diagnosis;(2)Multidisciplinary combined diagnosis(MDT);(3)IMPATT method diagnosis;(4)MDT+IMPATT method diagnosis.Four different diagnostic methods were compared with the Ghent II standard,and the diagnostic efficiency and accuracy of the four different diagnostic methods were compared.Results:1.Among the 147 participants included,36 cases of MFS were diagnosed by Ghent II standard revised in 2010,and the remaining 111 cases were non-MFS.2.DNA samples of 147 participants were tested by IMPATT detection kit.Among 36 MFS patients diagnosed by Ghent II standard,35 patients were detected to have gene mutation.According to the ACMG guidelines,29 patients(80.56%)were found to have positive mutation.Among them,there were 22 pathogenic genes and 7 suspected pathogenic genes,and the remaining 7 were classified as negative mutations with unknown significance.Two(6.90%)of the positive mutations were homozygous,and the remaining 27(93.10%)were heterozygous.The types of positive mutations included missense mutation in 26 cases(89.66%),loss of origin mutation in 2 cases(6.90%)and frameshift mutation in 1 case(3.45%).All negative mutations were heterozygous,including 6 missense mutations(20.69%)and 1 conservative non-frameshift loss mutation(3.45%).3.Single discipline detected 39 MFS cases(containing gold standard 12 cases),the detection rate of33.33%;MDT detected MFS 37 cases(28 cases containing gold standard),the detection rate of 77.78%;The IMPATT diagnostic kit detected 33 cases(29 cases containing gold standard),with a detection rate of 80.56%.The MDT+IMPATT detection kit detected 34 cases(32 cases containing gold standard),the detection rate was 88.89%.4.According to the data characteristics of this study,Mc Nemar test in paired chi-square was used for statistical analysis.The χ2 value was 1.132,P value was 0.287 and Kappa value was 0.088 after single department diagnosis and gold standard diagnosis.The value of χ2 was 70.054,P<0.001,and Kappa was 0.690.IMPATT assay kit diagnosis and gold standard diagnosis statistics showed that χ2 was92.462,P<0.001,and Kappa value was 0.792.The value of χ2 was 111.309,P<0.001,and Kappa was0.870.It can be seen that the detection kit diagnosis of MDT+IMPATT method has the highest consistency with the gold standard diagnosis.Conclusion:1.The detection rate of MFS using IMPATT assay kit was 80.56%,which was consistent with the gold standard diagnosis result.The diagnosis of MFS using IMPATT assay kit played an important role in the diagnosis.2.The detection rate of MDT+IMPATT combined detection kit in the diagnosis of MFS was 88.89%,which was the highest consistent with the diagnostic result of gold standard,and this method had the highest diagnostic value.3.IMPATT assay kit is worthy of promotion in clinical work,but it should be combined with MDT observation indicators.Only in this way can the detection rate of MFS be improved and the diagnosis of MFS be achieved quickly,accurately,conveniently and at a low cost.