Chuang Sm

Amniocentesis in mothers who are hepatitis B virus carriers does not expose the infant to an increased risk of hepatitis B virus infection

Sixty-seven pairs of mothers with hepatitis B virus (HBV) surface antigen (HBsAg) and their infants were divided into two study groups to determine the effect of amniocentesis on intrauterine HBV infection. In the first study group (35 pairs), the infants HBsAg status in cord blood was studied and the results were compared with those obtained in the cord blood from 65 infants born to HBsAg-positive women who did not have an amniocentesis. In the second study group (32 pairs), the HBV status of the infants was studied at the age of three months to five years and compared with the HBV status of 3,454 infants in the National HBV Prevention Program. In the first study group, one sample (2.9%) was weakly positive for HBsAg; while in the first control group, two (3.1%) were positive. In the second study group, three (10%) infants were positive for HBsAg. The failure rates of immunoprophylaxis in the second study and control groups were similar (9.4% vs 11% for HBsAg carrier mothers; 30% vs 14% for HBe antigen-positive carrier mothers). This suggested that genetic amniocentesis did not increase the risk of intrauterine HBV infection.

Molecular Characterization of β-Thalassemia in Taiwan and the Identification of two new Mutations

Polymerase chain reaction-based techniques were used to study the molecular defects of 480 unrelated beta-thalassemia heterozygotes in Taiwan. Analysis of artificially created restriction sites and gap-polymerase chain reaction were performed to detect four common mutations, i.e. IVS-II-654 (C-->T), codons 41/42 (-TCTT), codon 17 (A-->T), -28 (A-->G), and a deletional form of delta beta-thalassemia in the Chinese population. In cases with negative or ambiguous results with the aforementioned methods, direct DNA cycle sequencing using either S35-dATP or a fluorescent dye terminator, was carried out to determine the defects. A total of 14 different mutations have been found in this series. The IVS-II-654 mutation was the most common (39.6%), followed by the codons 41/42 mutation (37.9%). The four common genotypes accounted for 92.3% of defects. Two new mutations were detected: codon 31 (-C) and codons 40/41 (+T). Both defects resulted in a frameshift and a premature terminator, the former at codon 60, the latter at codon 43. Although we have studied our cases extensively, the molecular defects in seven alleles are still unknown.

Rapid Detection of Chinese Gγ+(Aγδβ)° -Thalassemia by Polymerase Chain Reaction

The Chinese G gamma+(A gamma delta beta)zero-thalassemia is caused by a deletion of more than 80 kilobases. It has a beta(+)-thalassemia phenotype and should be differentiated from other mutations causing beta-thalassemia. Using polymerase chain reaction with three oligonucleotide primers bridging the breakpoints, the deletion can be detected easily. The method is useful in the genetic counseling and prenatal diagnosis of the at-risk families.

Increased level of second trimester maternal serum chorionic gonadotropin in pregnancy with a fetus affected by homozygous alpha-thalassemia 1

With enzyme immunoassay, maternal serum chorionic gonadotropin (MShCG) level was determined in 58 pregnancies affected with fetal homozygous alpha-thalassemia 1. In 40 pregnancies with a gestational age of 10 to 14 weeks, 8 (20%) had an MShCG level above 2.5 multiples of the median (MoM); while in the other 18 pregnancies with a gestational age of 15 to 23 weeks, 14 (78%) had a level above 2.5 MoMs and none had a level below the median. Homozygous alpha-thalassemia 1 of the fetus was associated with an elevated MShCG. Therefore in second-trimester screening for Down’s syndrome by measurement of MShCG, homozygous alpha-thalassemia 1 should also be considered if elevated MShCG levels are found.

Prenatal diagnosis by transabdominal chorionic villus sampling in the second and third trimesters

From October 1989 through December 1993, 124 pregnant women (114 in the second trimester and 10 in the third trimester) underwent transabdominal chorionic villus sampling (CVS) for prenatal molecular or cytogenetic diagnosis. The mean gestational age was 18.2 weeks. Indications for CVS comprised single gene disease (72%), fetal anomalies detected by ultrasound (17%), advanced maternal age (6%), and previous siblings with chromosomal aberration (5%). Among the 89 fetuses at risk for single gene disease, 20 were diagnosed as affected by DNA analysis. Among the 35 fetuses at risk for chromosomal anomaly, 4 had trisomy, 3 had a 45, XO karyotype and 2 had a structural chromosomal abnormality. The miscarriage rate was 1.8% (2/114) and the spontaneous preterm birth rate was 2.4% (3/124). No maternal or other fetal complications occurred. This study suggested that second- and third trimester CVS is a safe and useful method for prenatal diagnosis.

Characterization of Chromosome Abnormality by Fluorescence in Situ Hybridization

The characterization of two chromosomal abnormalities was done by fluorescence in situ hybridization (FISH) using centromere-specific probes and chromosome-specific plasmid libraries. One case for prenatal diagnosis was shown to have 46, XY, dic (9). The pregnancy resulted in a normal male baby. The other case was an amenorrheic girl. Conventional cytogenetics showed 45, X/46, X, +mar. FISH revealed the marker chromosome was derived from X chromosome, thus 45, X/46, X, der (X). No SRY specific sequences were detected by polymerase chain reaction. After hormone replacement treatment, she had withdrawal bleeding. The application of FISH to cytogenetic diagnosis provides us a more accurate and rapid interpreatation of chromosome abnormalities, which is valuable in the genetic counseling of prenatal and postnatal cytogenetic diagnosis.