[Prenatal diagnosis of a case with X-linked spondyloepiphyseal dysplasia tarda].

OBJECTIVE: To analyze TRAPPC2 gene mutation in a family with X-linked spondyloepiphyseal dysplasia tarda and to provide genetic counseling and prenatal diagnosis. METHODS: All of 4 exons of the TRAPPC2 gene and their flanking sequences in the proband and her father were analyzed with polymerase chain reaction and direct DNA sequencing. Genomic DNA of the probands' fetus was extracted from amniotic fluid sampled at 18th gestational week. Gender of the fetus was determined by the presence of SRY gene. The sequence of fetal TRAPPC2 gene was also analyzed. RESULTS: A c.209G>A mutation was identified in exon 4 of the TRAPPC2 gene in the proband and her father. The fetus of was determined to be a male and also have carried the c.209G>A mutation. CONCLUSION: A c.209G>A mutation of TRAPPC2 exon 4 probably underlies the clinical manifestations in this family. The proband is a carrier, and her fetus is a male carrying the same mutation. Prenatal diagnosis is an effective method for the prevention of the disease.

Preliminary proteomic-based identification of a novel protein for Down's syndrome in maternal serum.

Prenatal screening for Down's syndrome (DS) is in need of improvement. As a powerful platform, proteomics techniques could also be used for identification of new biomarkers for DS screening. In this case-control proteome study, pregnant women were diagnosed prenatally by karyotype analysis from amniotic fluid (AF). Maternal serum samples were collected from six pregnancies with fetuses affected by DS and six pregnancies with normal fetuses. First, we used two-dimensional electrophoresis and mass spectrometry to identify the different levels of expression of proteins in maternal serum between the DS and control groups in the second trimester. Second, we used bioinformatics to analyze the proteins by DAVID. Then, the interesting candidates were further tested by enzyme-linked immunosorbent assay (ELISA). Twenty-nine proteins were successfully identified in maternal serum obtained from pregnancies with fetuses affected by DS. The top five proteins up-regulated were serotransferrin (TF), alpha-1b-glycoprotein (A1BG), desmin (DES), alpha-1-antitrypsin (SERPINA1) and ceruloplasmin (CP), while serum amyloid P-component (APCS) was the most down-regulated protein. These 29 proteins were categorized based on binding, catalytic activity and enzyme regulator activity. The biological roles were involved in biological regulation, metabolic processes, cellular processes and response to a stimulus. Based on ELISA, the median concentrations of CP and complement factor B (CFB) were 332.3 and 412.3 ng/mL, respectively. The concentrations of CP and CFB were significantly higher in the DS group than in the control group (P < 0.05). In conclusion, proteomic approaches offer the possibility of further improving the performance of DS screening and our identification of up- and down-regulated proteins may lead to new candidates for DS screening.

Bioinformatics characterization of differential proteins in serum of mothers carrying Down syndrome fetuses: combining bioinformatics and ELISA.

INTRODUCTION: Characterization of novel proteins in maternal serum derived from mothers carrying Down syndrome (DS) fetuses. MATERIAL AND METHODS: Based on last comparative proteomic analysis, five significant differences of expressed proteins in serum from four groups have been confirmed by ELISA. DAVID and GeneGo MetaCore were used to bioinformatically analyze candidate protein markers. RESULTS: The serum levels of ceruloplasmin (CP) and complement factor B (CFB) were significantly increased in mother carried DS fetuses (346.5 ng/ml and 466.8 ng/ml vs. 248.6 ng/ml and 293.5 ng/ml, p< 0.05). Twenty-nine proteins were mainly categorized into binding, catalytic activity and enzyme regulator activity proteins, and their biological roles were involved in biological regulation, metabolic processes, cellular processes, and response to stimuli. The immune response alternative complement pathway was the most significant GeneGo Pathway related to DS. CONCLUSIONS: These 29 proteins have relations with the development of Down syndrome, especially CP and CFB play more important roles.

Assessment of thyroid function during pregnancy: the advantage of self-sequential longitudinal reference intervals.

INTRODUCTION: To evaluate clinical value of a new self-sequential longitudinal reference intervals of thyroid function during pregnancy. MATERIAL AND METHODS: WE ESTABLISHED TWO DIFFERENT SERIES OF REFERENCE INTERVALS: self-sequential longitudinal reference intervals (SLRI) and general gestation-specific reference intervals (GSRI). For SLRI, the serum of 301 cases were collected five times in every case throughout the gestation. For GSRI, A total of 1455 subjects included in the study. We collected the serum respectively at various trimesters. We used TSH of both reference intervals to screen 1744 pregnant women, and compared the percentage of potential misclassification. RESULTS: Both SLRI and GSRI differed substantially from that for non-pregnant women (p < 0.05). There are similar fluctuations of serum TSH, FT4 and TPO-Ab during normal pregnancy. Although there were no significant differences in most reference intervals between SLRI and GSRI. But the IQR of SLRI were usually smaller than GSRI , especially in 1(st) trimester. Two hundred and fifty two women (14.4%) at various trimesters whose serum TSH concentration was within SLRI would be misclassified, while 23 women (1.3%) with a TSH concentration outside limit would not be identified. 0.11-3.84% women would got thyroid diseases during pregnancy. Subclinical hypothyroidism is most common maternal thyroid disorders. CONCLUSIONS: The SLRI can reflected the changes of thyroid function realistically, and can be used to decrease the percentage of potential misclassification of thyroid dysfunction during pregnancy. Screening for thyroid dysfunction of pregnant women is recommended and important.

Establishment of self-sequential longitudinal reference intervals of maternal thyroid function during pregnancy.

The objective of this study is to establish self-sequential longitudinal reference intervals of thyroid function in normal pregnant women. According to the selection criteria, 301 cases were taken as the normal pregnant population to establish a normal reference range. Meanwhile, 150 healthy women were selected as the normal non-pregnant control group. To establish their own self-sequential longitudinal reference intervals, we collected samples five times in every case throughout the gestation (including first trimester, second trimester, third trimester, prenatal and postpartum), and detected the levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase antibodies (TPO-Ab), and then established the self-sequential longitudinal reference intervals. The levels of TSH, FT4 and TPO-Ab were quantified by electrochemistry immunoassay (ECL) and statistically analyzed using SPSS 13.0 software. Serum TSH of normal pregnant women was at a low level in the first trimester (P < 0.05) and began to rise continuously. Not until prenatal phase was it restored to the non-pregnant state (P > 0.05). During pregnancy, serum FT4 of normal pregnant women were consistently lower than non-pregnant levels (P < 0.05) and kept at low levels. Serum TPO-Ab increased significantly in the third trimester and prenatal phase (P < 0.05). Of normal pregnant women, 6.5% were TPO-Ab positive. In conclusion, the reference intervals in our case will reflect the changes of thyroid function in pregnant women more realistically, resulting in a more accurate value for clinical diagnosis and therapy.