Assessment of a novel variation in DHODH gene causing Miller syndrome: The first report in Chinese population.

BACKGROUND: Miller syndrome is a rare type of postaxial acrofacial dysostosis caused by biallelic mutations in the DHODH gene, which is characterized mainly by craniofacial malformations of micrognathia, orofacial clefts, cup-shaped ears, and malar hypoplasia, combined with postaxial limb deformities like the absence of fifth digits. METHODS: In this study, a prenatal case with multiple orofacial-limb abnormities was enrolled, and a thorough clinical and imaging examination was performed. Subsequently, genetic detection with karyotyping, chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) was carried out. In vitro splicing analysis was also conducted to clarify the impact of one novel variant. RESULTS: The affected fetus displayed typical manifestations of Miller syndrome, and WES identified a diagnostic compound heterozygous variation in DHODH, consisting of two variants: exon(1-3)del and c.819 + 5G > A. We conducted a further in vitro validation with minigene system, and the result indicated that the c.819 + 5G > A variant would lead to an exon skipping in mRNA splicing. CONCLUSIONS: These findings provided with the first exonic deletion and first splice site variant in DHODH, which expanded the mutation spectrum of Miller syndrome and offered reliable evidence for genetic counseling to the affected family.

Clinical value of flow-mediated dilatation of brachial artery in hypertensive disorders complicating pregnancy.

Hypertensive disorders complicating pregnancy (HDCP) are common pregnancy-related disorders. In this study, we aimed to study the clinical value of flow-mediated dilation (FMD) in HDCP and its association with endothelial dysfunction and HDCP-related factors. 160 HDCP patients and 120 healthy pregnancies were enrolled in the study. The expressions of endothelial function markers and FMD were determined. In addition, their correlations in HDCP patients were also analyzed using Pearson's correlation analysis. FMD value decreased gradually from normal pregnancy to severe PE. The levels of plasma nitric oxidase (NO) were significantly lower in the HDCP group than those in the control group, while the levels of plasma endothelin-1 (ET-1) were increased dramatically in the HDCP group. Moreover, the levels of placental growth factor (PLGF) in HDCP women were significantly lower, while the soluble FMS-like tyrosine kinase 1 (sFLt-1) levels were markedly higher than those in control. In addition, the FMD value was correlated with the levels of plasma NO, ET-1, PLGF and sFlt1. It was also found that lower levels of FMD correspond to endothelial dysfunction and abnormal concentrations of PLGF and sFlt-1. The FMD value was associated with endothelial function indicators and could be a strong and non-invasive measure to predict HDCP. The association between the FMD values and endothelial function indicators in HDCP could be helpful for the prediction of pregnant hypertension more accurately.