PT  - JOURNAL ARTICLE
AU  - Bao, Minghui
AU  - Li, Ping
AU  - Li, Qifu
AU  - Chen, Hui
AU  - Zhong, Ying
AU  - Li, Shuangyue
AU  - Jin, Ling
AU  - Wang, Wenjie
AU  - Chen, Zhenzhen
AU  - Zhong, Jiuchang
AU  - Geng, Bin
AU  - Fan, Yuxin
AU  - Yang, Xinchun
AU  - Cai, Jun
TI  - Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting
AID  - 10.1136/jmedgenet-2019-106145
DP  - 2020 Aug 01
TA  - Journal of Medical Genetics
PG  - 571--580
VI  - 57
IP  - 8
4099  - http://jmg.bmj.com/content/57/8/571.short
4100  - http://jmg.bmj.com/content/57/8/571.full
SO  - J Med Genet2020 Aug 01; 57
AB  - Background Monogenic hypertension describe a series of hypertensive syndromes that are inherited by Mendelian laws. Sometimes genetic testing is required to provide evidence for their diagnoses, precise classification and targeted treatment. This study is the first to investigate the clinical utility of a causative gene screening and the combined yield of gene product expression analyses in cases with suspected monogenic hypertension.Methods We performed a large-scale multi-centre clinical genetic research of 1179 expertly selected hypertensive individuals from the Chinese Han population. Targeted sequencing were performed to evaluate 37 causative genes of potential cases of monogenic hypertension. Pathogenic and likely pathogenic variants were classified using the American College of Medical Genetics guidelines. Additionally, 49 variants of unknown significance (VUS) that had relatively high pathogenicity were selected and analysed using immunoblot protein expression assays.Results 21 pathogenic or likely pathogenic variants were identified in 33 of 1179 cases (2.80%). Gene product expression analyses showed 27 VUSs harboured by 49 individuals (4.16%) could lead to abnormally expressed protein levels. Consequently, combining genetic screening with gene product expression analyses increased the diagnostic yield from 2.80% to 6.79%. The main aetiologies established were primary aldosteronism (PA; 27, 2.29%) and pheochromocytoma and paraganglioma (PPGL; 10, 0.85%).Conclusion Molecular diagnoses obtained using causative gene screening combined with gene product expression analyses initially achieved a modest diagnostic yield. Our data highlight the predominant roles of PA and PPGL. Furthermore, we provide evidence indicating the enhanced diagnostic ability of combined genetic and functional evaluation.