Maternal plasma angiogenic and inflammatory factor profiling in foetal Down syndrome

<div><p>Objective and design</p><p>Angiogenic factors are proteins that are related to certain foetal chromosomal abnormalities. The aim of this study was to determine the concentration of 60 angiogenic factors in the plasma of women with offspring possessing trisomy 21/Down syndrome (DS).</p><p>Method</p><p>After analysing karyotyping results, we selected 20 patients with foetuses possessing DS, and for the control group, we selected 28 healthy patients with uncomplicated pregnancies who delivered healthy newborns at term (i.e., 15–18 weeks of gestation). To assess the concentration of proteins in the blood plasma, we used a protein macroarray which enabled simultaneous determination of 60 angiogenic factors per sample.</p><p>Results</p><p>We observed a statistically significant increase in the concentration of these five angiogenic and inflammatory factors: TGFb1 (p = 0.039), angiostatin (p = 0.0142), I-309 (p = 0.0476), TGFb3 (p = 0.0395), and VEGF-D (p = 0.0173)—compared to concentrations in patients with healthy foetuses.</p><p>Conclusion</p><p>Our findings suggest that angiogenic factors may play role in DS pathogenesis.</p></div

The ROC curves for concentration of sphingolipids in plasma: C22-Cer and C24:1-Cer.

<p>The area under the ROC curve for C22-Cer was 0.814 and for C24:1-Cer it was 0.729. AUC- Area under curve; ROC- Receiver operating characteristic.</p

Concentrations of angiogenic factors in maternal plasma.

<p>Concentrations of angiogenic factors in maternal plasma.</p

Diagnostic values of sphingolipids in amniotic fluid.

<p>Diagnostic values of sphingolipids in amniotic fluid.</p

The list of quantified sphingolipids with the limit of detection.

<p>The list of quantified sphingolipids with the limit of detection.</p

Clinical characteristic of the patients.

<p>SD—standard deviation</p><p>Clinical characteristic of the patients.</p

Sensitivity and specificity of biomarkers in plasma: C22-Cer and C24:1-Cer.

<p>We demonstrated a significantly higher risk of Down Syndrome when the plasma concentration of C22-Cer > 12.66 ng/100ul (sens. 0.9, sp. 0.79, <i>P value =</i> 0.0007) and C24:1-Cer > 33,19 ng/100ul (sens. 0.6, sp. 0.86, <i>P value =</i> 0.0194).</p

Diagnostic values of sphingolipids in plasma.

<p>Diagnostic values of sphingolipids in plasma.</p

Segregation of Kallmann Syndrome and the <i>PROKR2</i> or <i>PROK2</i> Mutations in Affected Families

<p>Filled symbols denote clinically affected individuals with both hypogonadism and anosmia (or hyposmia). Half-filled symbols denote individuals with either anosmia only (right black part) or hypogonadism only (left black part). Genotypes, if available, are indicated below. The symbol + denotes normal allele, and fs stands for frameshift mutation. In several pedigrees the mutation is associated with varying phenotypes. Notably, in family A the disease apparently segregates according to a semi-dominant mode of transmission. The schematic representation of PROKR2 shows the locations of the nine missense mutations found in familial and non-familial KS cases, with respect to the putative N-terminal (N ter), C-terminal (C ter), extracellular loop (e1-e3), intracellular loop (i1-i3), and transmembrane (T1–T7) domains [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020175#pgen-0020175-b013" target="_blank">13</a>] of this G protein-coupled receptor.</p