Comprehensive maternal serum proteomics identifies the cytoskeletal proteins as non-invasive biomarkers in prenatal diagnosis of congenital heart defects.
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ABSTRACT:
SUBMITTER: Chen L
PROVIDER: S-EPMC4707500 | biostudies-literature | 2016 Jan
REPOSITORIES: biostudies-literature
Publications
Comprehensive maternal serum proteomics identifies the cytoskeletal proteins as non-invasive biomarkers in prenatal diagnosis of congenital heart defects.
Chen Lizhu L Gu Hui H Li Jun J Yang Ze-Yu ZY Sun Xiao X Zhang Li L Shan Liping L Wu Lina L Wei Xiaowei X Zhao Yili Y Ma Wei W Zhang Henan H Cao Songying S Huang Tianchu T Miao Jianing J Yuan Zhengwei Z
Scientific reports 20160111
Congenital heart defects (CHDs) are the most common group of major birth defects. Presently there are no clinically used biomarkers for prenatally detecting CHDs. Here, we performed a comprehensive maternal serum proteomics assessment, combined with immunoassays, for the discovery of non-invasive biomarkers for prenatal diagnosis of CHDs. A total of 370 women were included in this study. An isobaric tagging for relative and absolute quantification (iTRAQ) proteomic approach was used first to com ...[more]
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Project description:The multiple endocrine neoplasia type 2A (MEN2A) is a monogenic disorder characterized by an autosomal dominant pattern of inheritance which is characterized by high risk of medullary thyroid carcinoma in all mutation carriers. Although this disorder is classified as a rare disease, the patients affected have a low life quality and a very expensive and continuous treatment. At present, MEN2A is diagnosed by gene sequencing after birth, thus trying to start an early treatment and by reduction of morbidity and mortality. We first evaluated the presence of MEN2A mutation (C634Y) in serum of 25 patients, previously diagnosed by sequencing in peripheral blood leucocytes, using HRM genotyping analysis. In a second step, we used a COLD-PCR approach followed by HRM genotyping analysis for non-invasive prenatal diagnosis of a pregnant woman carrying a fetus with a C634Y mutation. HRM analysis revealed differences in melting curve shapes that correlated with patients diagnosed for MEN2A by gene sequencing analysis with 100% accuracy. Moreover, the pregnant woman carrying the fetus with the C634Y mutation revealed a melting curve shape in agreement with the positive controls in the COLD-PCR study. The mutation was confirmed by sequencing of the COLD-PCR amplification product. In conclusion, we have established a HRM analysis in serum samples as a new primary diagnosis method suitable for the detection of C634Y mutations in MEN2A patients. Simultaneously, we have applied the increase of sensitivity of COLD-PCR assay approach combined with HRM analysis for the non-invasive prenatal diagnosis of C634Y fetal mutations using pregnant women serum.
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