Identifying new potential genetic biomarkers for HELLP syndrome using massive parallel sequencing

Area of Science:

• Genetics
• Molecular Biology
• Obstetrics

Background:

• Preeclampsia (PE) affects ~5% of pregnancies.
• HELLP syndrome (haemolysis, elevated liver enzymes, low platelet) is a life-threatening complication of PE.
• The genetic basis of HELLP syndrome remains largely unknown due to the complexity of involved genes.

Purpose of the Study:

• To identify novel genes and mutations associated with HELLP syndrome.
• To discover potential biomarkers for HELLP syndrome.
• To investigate the genetic underpinnings of HELLP syndrome.

Main Methods:

• Whole-exome sequencing was performed on 79 unrelated HELLP patients.
• A control group of 176 individuals was used for variant screening.
• Bioinformatics filters and in silico mutation modeling were employed to analyze sequence variants in 487 genes.

Main Results:

• Numerous sequence variants were found in genes regulating angiogenesis, coagulation, blood pressure, cell processes, and immunity.
• Five variants caused premature stop codons in critical placental genes (STOX1, PDGFD, IGF2, MMP1, DNAH11).
• Six variants destabilized protein structures, and 57% of patients had at least two mutations, indicating a polygenic origin.

Conclusions:

• Novel genetic insights into the origin of preeclampsia and HELLP syndrome were uncovered.
• Identified genetic variants represent potential novel biomarkers for HELLP syndrome.
• These findings may have significant clinical utility in managing PE/HELLP.