Abstract
BackgroundThis study wants to know the genetic cause of preeclampsia (PE) which is a leading cause of maternal and perinatal death, but the underlying molecular mechanisms that cause PE remain poorly understood. Many single nucleotide polymorphisms have been identified by genome-wide association studies and were found to be associated with PE; however, few studies have used whole-exome sequencing (WES) to identify PE variants.MethodsFive patients with severe early-onset preeclampsia (EOPE) were recruited, and WES was performed on each patient. Sanger sequencing was used to confirm the potential causative genetic variant.ResultsAfter a stringent bioinformatics analysis, a rare variant in the GOT1 gene, c.44C > G:p.P15R, was found in one patient. Bioinformatics analysis showed that the variant site is highly conserved across several species and was predicted to be a pathogenic variant according to several online mutational function prediction software packages. Further structural biology homology modeling suggested that P15R would change the electric environment of enzymatic center, and might affect the binding affinity of substrate or product.ConclusionWe demonstrated for the first time that the variant in GOT1 may be associated with EOPE, the results of this study provide researchers and clinicians with a better understanding of the molecular mechanisms that underlie maternal severe EOPE.
Highlights
This study wants to know the genetic cause of preeclampsia (PE) which is a leading cause of maternal and perinatal death, but the underlying molecular mechanisms that cause PE remain poorly understood
We only identified a rare variant of the Glutamate oxaloacetate transaminase 1 (GOT1) gene c.44C > G:p.P15R in Patient No 1 (P1); the variant was confirmed by Sanger sequencing (Fig. 1a)
We speculated that genetic factors may play an important role in patients with severe Early-onset preeclampsia (EOPE); whole-exome sequencing (WES) was performed for each patient
Summary
This study wants to know the genetic cause of preeclampsia (PE) which is a leading cause of maternal and perinatal death, but the underlying molecular mechanisms that cause PE remain poorly understood. Preeclampsia (PE) is a pregnancy-specific multi-systemic syndrome that affects several organs, including the kidneys, liver, and brain, and is a leading cause of maternal and perinatal morbidity and mortality. Genetic alteration is one of the main causes of PE [9,10,11], but the exact underlying molecular mechanism remains unclear. Genome-wide association studies and Sanger sequencing are frequently used in the genetic analysis of PE, while high-throughput sequencing technology such as wholeexome sequencing (WES) is rarely used to find the genetic cause of PE. A novel variant in GOT1 was identified in one patient (P1), and is considered to be a potentially pathogenic variant associated with PE, according to in silico analysis and structural biology predictions
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