A toolkit for providing early diagnosis and individualized drug therapy for monogenetic hypertension through exomic re-sequencing

摘要

#$%^&*AU2019101134A420191031.pdf#####Abstract A toolkit for providing early diagnosis and individualized drug therapy for monogenetic hypertension through exotic re-sequencing is disclosed in this application. Monogenic hypertension is a serious form of hypertension characterized by early-onset and an incremental risk of cardio-cerebrovascular disease and renal disease. Clinical diagnosis of monogenic hypertension is often challenged by incomplete or overlapping clinical manifestation and requirement of genetic evidence. Here, a detailed clinical diagnosis process for monogenic hypertension was designed on the basis of Whole Exome Sequencing (WES). The evaluation criterion panel used in this diagnosis was built by pathogenic 102 single-nucleotide polymorphisms (SNPs) that can lead to monogenetic hypertension, they are selected based on their clinical significance in National Centre for Biotechnology Information website (NCBI) and PharmGKB databases. 1. Patients' exome were produced via high-throughput sequencing and the quality of the sequencing was evaluated by FastQC. 2. Software such as Burrows-Wheeler Aligner (BWA) and Genome Analysis Toolkit (GATK) were used to detect the disease-associated SNPs. 3. The detected mutated sites can be annotated to produce a reliable report for the patient. By identifying and listing the 1protein change, the report can provide clinicians with valuable information for effective individualized therapeutic option. Moreover, the anti-monogenic hypertensive drugs that specifically restore the pathway disturbed by these SNP and their proven target mutation points were summarized as a guid for precise medication. It can be used together with the genetic screening penal to greatly facilitate the treatment of monogenic hypertension. 2Literature research on various monogenic Literature hypertensions Examination of conditions of monogenic OMIMNCBI hypertensions using data from OMIM Match information on Search for medical NCBI to identify the healing plan refers to genomic locations of different types of PharmGKB variants monogenic Liddle syndrome Record information Congenital adrenal hyperplasia and divide the whole Syndrome of apparent mineralocorticoid excess(AME) based on conditions Geller syndrome Gordon syndrome Familial hyperaldosteronism type I Familial hyperaldosteronism type II Make a summarized FamilialhyperaldosteronismtypeIII chart Familial hyperaldosteronism type IV Familial pheochromocytoma Hypertension and Brachydactyly Syndrome Pseudohypoaldosteronism type IIE; PHA2E Figure 1 1