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In candidate gene era, dozens of single-nucleotide polymorphisms (SNPs) within renin-angiotensin-aldosterone system (RAAS) have been reported to be significantly associated with hypertension. However, the unbiased genome-wide association studies (GWAS) rarely identified the SNPs within RAAS were associated with hypertension or blood pressure (BP) traits. In order to figure out whether genetic polymorphisms of RAAS are really associated with hypertension, we systemically searched the GWAS Catalogue and identified all the known RAAS genes and relevant diseases/traits. After data processing, we found that polymorphisms within REN, AGT, ACE2, CYP11B2, ATP6AP2 and HSD11B2 were not associated with any disease or trait. SNPs within ACE, AGTR1, AGTR2, MAS1, RENBP and NR3C2 were associated with other diseases or traits, but showed no direct connection with hypertension. The only SNP associated with a BP trait, systolic BP was rs17367504. However, it is located in the intronic region of MTHFR near many plausible candidate genes, including CLCN6, NPPA, NPPB and AGTRAP. Therefore, the effect of RAAS polymorphisms may have been overestimated during the 'candidate gene era'. In the time of 'precision medicine', the power of RAAS variants needs to be reconsidered when evaluating one's susceptibility of hypertension.

Stargardt disease (STGD1) is a juvenile macular degeneration predominantly inherited in an autosomal recessive pattern, characterized by decreased central vision in the first 2 decades of life. The condition has a genetic basis due to mutation in the ABCA4 gene, and arises from the deposition of lipofuscin-like substance in the retinal pigmented epithelium (RPE) with secondary photoreceptor cell death. In this study, we describe the clinical and genetic features of Stargardt patients from four unrelated Chinese cohorts. The targeted exome sequencing (TES) was carried out in four clinically confirmed patients and their family members using a gene panel comprising 164 known causative inherited retinal dystrophy (IRD) genes. Genetic analysis revealed eight ABCA4 mutations in all of the four pedigrees, including six mutations in coding exons and two mutations in adjacent intronic areas. All the affected individuals showed typical manifestations consistent with the disease phenotype. We disclose two novel ABCA4 mutations in Chinese patients with STGD disease, which will expand the existing spectrum of disease-causing variants and will further aid in the future mutation screening and genetic counseling, as well as in the understanding of phenotypic and genotypic correlations.

Choroideremia is a bilateral and progressive X-linked inherited disease characterized by widespread chorioretinal atrophy with relative sparing of the macular region. It is caused by mutations in the ubiquitously expressed CHM gene, which lead to the absence of the Rab escort protein 1 (REP-1), resulting in prenylation deficiency. Typical fundus appearances for choroideremia were found in 3 probands from three unrelated Chinese families in our study. We firstly used the targeted exome sequencing (TES) technology to detect mutations in CHM gene. Based on an established filtering strategy of data analyses, along with confirmation by co-segregation, a previously reported mutation (c.1584_1587del TGTT, p.V529Hfs*7) was identified in one family, while two novel mutations (c.227_232delinsTGTCATTTCA, p.Q76Lfs*7; c.710dupA, p.Y237_S238delinsX) were identified in the other two families. These findings not only expands the currently limited spectrum of Chinese disease-causing variants in CHM gene, but also increases our understanding of the phenotypic and genotypic correlations of choroideremia, and may potentially lead to improved genetic counseling and specific treatment for families with choroideremia as well.