[Analysis of relationship between patients with chromosomal translocation and the outcome of pregnancy].

OBJECTIVE: To explore the relationship between chromosome translocation and their phenotypic effect by analyzing the patients with loss pregnancy and avoiding fetuses with chromosomal abnormalities. METHODS: A total of 3067 cases with infertility or loss pregnancy were recruited to receive chromosome examination during January 2005 to December 2011 at Center of Prenatal Diagnosis, Peking University People's Hospital. Retrospective study was used to analyze the chromosome karyotypes and infertility or loss pregnancy. RESULTS: In 72 cases of patients with chromosome translocation, there were 17 pregnancies with homology translocation in fetus. And the numbers of patients with loss pregnancy and sex apparatus malformations were 40 and 15 respectively. CONCLUSION: Chromosome translocation plays an important role in patients with loss pregnancy or infertility. And chromosome examination should be performed to exclude the possibility of chromosome abnormities in patients with obstinate infertility.

Cytogenetic analysis of 355 cases of fetal loss in different trimesters.

OBJECTIVE: We estimated the success rates of cytogenetic analyses in different tissue samples after intrauterine fetal deaths and analyzed the value of cytogenetic testing for determining the causes. METHODS: Women with intrauterine fetal deaths (occurring at > 10 weeks of gestation) were offered either invasive testing before medical induction of labor, or solid tissue biopsy diagnosis after delivery. RESULTS: A total cohort of 355 intrauterine fetal deaths was studied. During antepartum examinations, invasive procedures included amniocentesis (AMC), chorionic villus sampling (CVS) and umbilical cord (UBC) sampling. During postpartum examinations, samples were taken from unfixed specimens of fetal skin, placenta and other tissues. Chromosomal abnormalities were observed in 22 fetal deaths for which cytogenetic analyses were successful. Logistic regression analysis identified antepartum invasive sampling [P = 0.000, odds ratio (OR) 31.125, 95% confidence interval (CI) 14.265-67.908] to be associated with a high cytogenetic success rate and older age with fetal deaths (P = 0.104, OR 0.487, 95% CI 0.204-1.160) not to be associated with a high chromosomal abnormality. In the patients with recurrent pregnancy loss, the chromosomal abnormality rate of 18.6% of spontaneous abortions has not been significantly more than that of fetal deaths 11.5% (P = 0.437). CONCLUSION: Parents should be counseled on all aspects of cytogenetic analysis after fetal death. Antepartum testing after pregnancy loss is recommended.

[Molecular and prenatal diagnosis of a pedigree with spinocerebellar ataxia].

OBJECTIVE: To identify the type of a pedigree with spinocerebellar ataxia, and carry out asymptomatic carrier detection and prenatal diagnosis. METHODS: The blood samples of two patients in the spinocerebellar ataxia pedigree were collected. Based on the clinical characteristics of the pedigree and the disease incidence in China, the regions containing the CAG repeat of the SCA1, SCA2 and SCA3/MJD genes were amplified by polymerase chain reaction (PCR). The numbers of CAG repeats in the normal and abnormal allele fragments were identified by using agarose gel electrophoresis and DNA sequencing. We further carried out tests on the children of the patients and fetus to identify the presence of the abnormal allele. RESULTS: The numbers of CAG repeat in the SCA1 and SCA2 genes were in the normal range. The CAG repeat number in one allele of SCA3/MJD gene was in the normal range, while that in the other allele was in the abnormal range. One of the children of the patients and the fetus carried the abnormal allele. CONCLUSION: It was confirmed that the pedigree was SCA3/MJD by gene diagnosis. One of the children of the patients was asymptomatic carrier and the fetus also carried the abnormal allele.

[Chromosome abnormalities and congenital heart diseases: a retrospective on 49 cases].

OBJECTIVE: To investigate the association between congenital heart diseases and chromosome abnormalities. METHODS: Patients with congenital heart diseases who underwent chromosome examinations during Jan 2006 and Dec. 2009 in the Center of Prenatal Diagnosis of Beijing University People's Hospital were recruited in the study. The association between chromosome karyotypes and types of congenital heart diseases was analyzed. RESULTS: Among the 49 patients with congenital heart diseases, trisomy 21 was established in 11 cases, trisomy 18 in 6 cases, trisomy 13 in 6 cases, trisomy 14 in 1 cases, trisomy 16 in 3 cases, trisomy 8 in 1 cases, trisomy 22 in 1 cases, sex chromosomal abnormalities in 8 cases, triploid in 2 cases, partial chromosomal trisomy in 8 cases, and 46,XX/XY, 5p-- in 2 cases. CONCLUSION: Chromosome abnormalities are associated with congenital heart diseases. Different abnormal chromosome karyotypes contribute to different types of congenital heart diseases. Prenatal chromosome examinations could be undertaken to detect congenital heart diseases.

[Gene diagnosis for spinal muscular atrophy and its application study].

OBJECTIVE: To establish an effective testing system for gene diagnosis, carrier detection and prenatal diagnosis for spinal muscular atrophy (SMA). METHODS: Twenty-six patients with SMA were directly tested with PCR-RFLP for exon 7 deletion in the SMN1 gene. Carrier detection was carried out with multi-PCR-DHPLC. Amniotic fluid was taken at the middle stage of gestation from pregnant women who had given birth to affected children. RESULTS: Twenty-five out of 26 patients were diagnosed as having SMN1 gene deletion. Fifty-two of their parents were found to be carriers of exon 7 deletion. Eight of 20 fetuses were diagnosed as having SMN1 gene deletion by PCR-RFLP. CONCLUSION: PCR-RFLP and multi-PCR-DHPLC techniques can provide rapid diagnosis for exon 7 deletion detection and carrier detection. PCR-RFLP may also be adapted for prenatal gene diagnosis of exon 7 deletion in SMN1 gene.

[Application study on inversion diagnosis of F8 gene in hemophilia A].

OBJECTIVE: To establish an effective method of genetic diagnosis on hemophilia A (HA) by detecting the inversion mutation in intron 22 of F8 gene. METHODS: Intron 22 inversion mutation in F8 gene was detected by using long distance-polymerase chain reaction (LD-PCR) and inversion-PCR (I-PCR) in 31 HA patients. The mothers of HA patients with intron 22 inversion mutation were selected to carrier diagnosis and amniotic fluid of the pregnant women with inversion mutation was collected at intermediate stage of gestation, and used to prenatal genetic diagnosis. RESULTS: Seven patients showed F8 gene inversion mutation in thirty-one patients. Three in four mothers of HA patients with intron 22 inversion mutation were diagnosed as carriers. The prenatal diagnosis result indicated that the fetus conceived in the HA-carrier woman was normal individual. CONCLUSION: The detection of intron 22 inversion mutation by LD-PCR and I-PCR is time-saving, and can be used in prenatal diagnosis on HA.

Prenatal cytogenetic diagnosis study of 2782 cases of high-risk pregnant women.

BACKGROUND: Prenatal diagnoses are extremely advantageous for pregnant women with high-risk indicators and can help prevent the birth of malformed infants. However, no large-scale statistical study analyzing the correlation between fetal chromosome disorders and abnormal indicators during pregnancy has been done in China. The objectives of this study were to diagnose and analyze fetal chromosome abnormalities, determine the feasibility of the various prenatal test methods and establish diagnostic guidelines for the early, middle, and late trimesters. METHODS: From January 2004 to May 2009, 2782 pregnant women at high-risk underwent prenatal diagnoses. Categorized data expressed as either actual counts or percentages were analyzed by the chi-square or Fisher's exact test. Chorionic villus sampling was performed in the early-trimester (10 - 12 weeks of gestation), amniocentesis in mid-trimester (16 - 28 weeks of gestation), and umbilical cord blood collection in mid- or late-trimester (16 - 37 weeks of gestation). In 51 cases either autopsy samples from intrauterine fetal deaths or placental tissues from aborted fetuses were tested. RESULTS: Chromosomal abnormalities were observed in 3.99% (111/2782) of the samples. Overall, the success rate of cytogenetic analysis for high-risk pregnancy groups was 98.17% (2731/2782). It was significantly less successful when used to analyze data from the chorionic villus sampling compared with that from amniocentesis and umbilical cord blood (P = 0.000). Abnormal chromosome carriers had the highest percentage of abnormal chromosomes (67.86%) when compared with chromosomal abnormalities in patients with ultra-sonographic "soft markers" (11.81%), advanced maternal age (4.51%) and those who had positive serum screening results (P = 0.000). CONCLUSIONS: Invasive prenatal diagnostic techniques are feasible tools for confirming fetal chromosomal abnormalities. Abnormal chromosomes detected in one of the parents carrying abnormal chromosome, ultrasound soft markers, advanced maternal age or positive serum screening results were associated with a higher frequency of fetal genetic diseases.