Objective To evaluate the efficiency of combined screening for chromosomal abnormalities in the first trimester and the ultrasound characteristics of these fetuses.Methods Retrospective study for 5000 singleton pregnancies by combined screening of trisomies 21,18,13 and Turner syndrome.Risk algorithms were developed for calculation of patient-specific risks for each of the three trisomies based on maternal age,fetal nuchal translucency,free β human chorionic gonadotropin and serum pregnancy associated plasma protein A at 11 to 13 +6 weeks of pregnant.The value of nuchal translucency (NT) and β-hCG and pregnancy-associated plasma protein A (PAPP-A) level were inputted computer,and calculate the risk value (≥ 1 ∶ 270) by automatic analysis software.Two hundred and four cases with high risk were performed transabdominal chorionic villus biopsy to detect the fetal chromosomal karyotypes.Meanwhile,other ultrasonic characteristics of fetal were elevated.Results (1) Five thousand cases of pregnant women were detected,including 4983 normal cases,62 cases were induced labor for a variety of reasons in the second trimester,including 40 cases with normal karyotype but with congenital heart disease,17 cases of chromosome abnormalities (9 cases trisomy 21,2 cases trisomy 18,1 cases trisomy 13,4 cases 45X),2 cases spina bifida,2 cases digestive tract obstruction,1 cases giant bladder.One case with low risk of fetal chromosomal abnormalities in combined screening,but high risk of age (maternal age were over 40 years old),it was 21 trisomy syndrome after the prenatal diagnosis.(2) Five cases of nasal bone loss in 9 cases of trisomy 21 (5/9),5 cases with three tricuspid regurgitation (5/9),4 cases of venous ductus a wave flow reverse (4/9),3 cases of fetal nasal bone loss accompanied by tricuspid regurgitation and venous ductus a wave flow reverse (3/9).One case of nasal bone loss in 2 cases of trisomy 18,2 cases were tricuspid regurgitation and venous ductus a wave flow reverse.Two cases in 4 cases of 45X had venous ductus a wave flow reverse.There were 8 cases (0.16％) nasal bone absence in 4983 cases of normal karyotype fetus,48 cases (0.96％) of tricuspid regurgitation and 44 cases (0.88％) of venous ductus a wave flow reverse.Thirty-two cases in 40 cases (80％) of fetal congenital heart disease were tricuspid regurgitation,30 cases of venous ductus a wave flow reverse (75％).Eight cases of nasal bone absence normal karyotype fetus were found the nasal bone at 20 weeks gestation.Conclusion Combination screening of nuchal translucency with serum markers in the first trimester were high detection rate and low false positive rate; a wave reversion and fetal nasal bone absence accompanied by tricuspid regurgitation can improve the detection rate of abnormal karyotype; abnormalities ultrasound marker may be associated with fetal congenital heart disease at 11-13 +6 weeks of pregnancy.

Objective To assess the clinical value of fetal chromosomal aneuploidy diagnosed by free fetal DNA in maternal plasma in 11-13+6 gestational weeks.Methods A total of 2 650 pregnant women who had prenatal care in Tianjin Center Hospital of Obstetrics and Gynecology from January 1,2010 to December 31,2010 were included.Each of them had an ultrasound scan to measure fetal nuchal translucency thickness.Maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein A test was performed as part of screening for chromosomal abnormalities.Results of ultrasound and maternal plasma biochemical analysis were entered into the database,and converted into multiple of median (MoM) by factors such as maternal age,weight,ethnicity,smoking history and mode of conception.The cutoff value was 1 ∶ 270.Meanwhile,20 cases had cell free fetal DNA (cffDNA) test and the ratio of the single nucleotide polymorphism on two alleles of plancenta-specific 4 (PLAC4) were measured in 16 cases.T-test,rank sum test,MannWhitney U test and Chi-square test were used as statistical methods.Results (1) A total of 74 cases were judged as high-risk,among which 35 cases underwent transabdominal chorionic villus sampling (18 cases had cffDNA test),37 cases underwent amniocentesis at the week of 20,and two cases of Rh negative did not receive the invasive examination.Totally 20 cases,including two Rh negative cases,had the cell-free fetal DNA test.(2) By cffDNA test of maternal plasma,two cases of 21 trisomy,one case of 18 trisomy,two cases of 45,XO and one case of balanced translocation were diagnosed.(3) In the two cases of 21 trisomy,maternal plasma G/A ratio ofPL4C4 RNA-single nucleotide polymorphism alleles was 1.00 (0.98,1.02) ; in 14 pregnancies with normal chromosome,the ratio was 1.055 (1.02,1.13,Z=3.5).There was no significant difference (P=0.066).Conclusion Diagnosing of fetal chromosomal aneuploidy by cffDNA in maternal plasma is feasible and noninvasive with high negative predictive value,and can be used in Rh-negative pregnant women for prenatal screening and diagnosis.

Objective To explore the genetic pathogen of patients with non-syndromic hearing impairment and to provide prenatal diagnosis for the families of hereditary deafness. Methods Mutation screening of GJB2, SLC26A4, GJB3 and mitochondrial 12 S rRNA genes was performed in 208 patients with non-syndromic hearing impairment by gene chip. Then direct sequencing was used in 41 patients who were found one mutation of GJB2 or SLC26A4 gene. And prenatal diagnosis was carried out in two families by direct sequencing. Results Eighty-six patients (41.35％) were found at least one mutation by gene chip. Among them, 40 patients were found to carry two mutations and 46 patients were found to carry one mutation. The most frequent mutation was 235delC, which was found in 46 patients. And 12 cases were found the second mutation through direct sequencing. A total of 52 (25.00％) patients were detected two mutations. Prenatal diagnosis showed that one fetus carried compound mutations of 299-300delAT and 235delC, and another one carried heterozygous mutation of IVS7-2A>G. Conclusion Patients with non-syndromic hearing impairment can be accurately diagnosed by gene chip and Sanger sequencing. The prenatal diagnosis is primary means for high-risk fetuses.

OBJECTIVETo compare villus cell culture and karyotype analysis with single nucleotide polymorphism (SNP) microarray technology for the detection of chorionic villus chromosome in patients with retention of abortion.

METHODSForty cases were analyzed with the two methods.

RESULTSChorionic villus culturing was successful in 29 cases, among which 10 were found to have an abnormal karyotypes. For the SNP microarray analysis, all 40 cases were successful, among which 16 were shown to have an abnormal molecular karyotype.

CONCLUSIONSNP microarray technology is highly accurate and specific, which is particularly suitable for the detection of chromosomal deletions or duplications, uniparental disomy, low-percentage mosaicism and other chromosomal abnormalities. It has provided an effective supplement to the conventional chorionic villus culture and karyotype analysis.

Abortion, Missed ; genetics ; Adult ; Chorionic Villi ; chemistry ; Chromosome Aberrations ; Female ; Humans ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Polymorphism, Single Nucleotide ; Pregnancy ; Pregnancy Trimester, First ; genetics