Prenatal diagnosis of fragile x syndrome: (cgg)n expansion and methylation of chorionic villus samples

Fragile X syndrome is the most common form of inherited mental retardation, due to an expansion of the (CGG)_n trinucleotide repeat in the FMR-1 gene and hypermethylation of its 5′ upstream CpG island. Two major problems remain to be resolved for fragile X prenatal diagnosis: the abnormal methylation patterns of chorionic villus samples (CVS) and the inability to predict the mental status of females with the full mutation. We present here the results of ten prenatal diagnoses of fragile X syndrome using Southern blotting and polymerase chain reaction (PCR) amplification, and the analysis of 50 further CVS to test the methylation status of the CpG island of the FMR-1 gene. In the ten ‘at-risk’ CVS, eight normal (five males and three females) and two affected male fetuses were detected. Absence of methylation in the CVS was observed in two cases, which was not found upon subsequent examination of the newborn or of fetal tissues. In the 50 CVS not ‘at risk’ for fragile X syndrome, abnormal fragment patterns for probe StB12.3 were detected in 32 per cent for female and 24 per cent for male fetuses. This abnormal pattern could be due to absent or partial methylation of the CpG island of the FMR-1 gene in chorionic villus tissues.     

Down's syndrome screening in multiple pregnancies using alpha-fetoprotein and free beta hCG

Second-trimester distributions of the free beta human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) levels in 420 twin and 19 triplet pregnancies were measured and compared with the distributions in 6661 singleton pregnancies. On average, the levels of both analytes were twice as high in twins and over three times as high in triplets. Eight sets of twins discordant for Down's syndrome showed elevated levels of free beta hCG and reduced levels of AFP after correction of the multiple of the median for the presence of a twin pregnancy. Screening for Down's syndrome using the twin correction of the multiple of the median is expected to achieve a 51 per cent detection rate at a 5 per cent false-positive rate using these two markers.     

The prenatal diagnosis of joubert's syndrome of familial agenesis of the cerebellar vermis

The prenatal diagnosis by ultrasound examination of Joubert's syndrome of familial agenesis of the cerebellar vermis is described allowing termination of pregnancy ai 26 weeks gestation. The diagnosis was made by a comparison of the prenatal ultrasound examination with computerized axial tomography obtained from the siblings with the same condition.     

First-trimester maternal serum human chorionic gonadotrophin as a marker for fetal chromosomal disorders

The Dutch Working Party on Prenatal Diagnosis has initiated a study on the possibilities of first-trimester screening for fetal chromosomal disorders. We report on maternal serum human chorionic gonadotrophin (MS-hCG) measurements in 1348 pregnancies with a chromosomally normal fetus and 53 pregnancies with a chromosomally abnormal fetus. The median MS-hCG concentration in 24 pregnancies with Down's syndrome was 1.19 multiples of the normal median (MoM). The MS-hCG distributions in normal and Down's syndrome pregnancies did not differ significantly (t-test: t = 1.945, p >0.05). We also found no difference between normal pregnancies and pregnancies with other chromosomal disorders (six cases of trisomy 18, MoM = 0.80; four cases of sex chromosome abnormality, MoM = 1.01; 17 cases of chromosomal mosaicism in chorionic villi, MoM = 1.11). Selecting an upper limit at the 90th centile could detect 25 per cent of pregnancies with Down's syndrome. We conclude that, in the first trimester, MS-hCG as a screening factor for Down's syndrome is of minor value. However, MS-hCG could be a useful factor in a first-trimester screening programme based on a combination of markers.     

Birth prevalence of down's syndrome in England and Wales

The natural birth prevalence of Down's syndrome for England and Wales in 1974–1987 (i.e., the birth prevalence in the absence of prenatal diagnosis and the induced abortion of affected pregnancies) was estimated by applying the maternal age-specific birth prevalence derived from epidemiological studies to the number of births in single-year age groups tabulated by the Office of Population Censuses and Surveys (OPCS). On average, the natural birth prevalence was 12.6 per 10 000 births and increased slightly from 12.2 to 13.2 per 10 000 births over the 14-year period. Using data on induced abortions carried out on account of Down's syndrome reported to OPCS under the statutory abortion notification scheme, 14 per cent of affected births were avoided by the induced abortion of affected pregnancies, so that the actual birth prevalence of Down's syndrome was estimated at 10.8 per 10000 births. Using data on Down's syndrome births reported to OPCS under the voluntary congenital malformation notification scheme, the prevalence was 7.2 per 10000 births, so only 67 per cent of the estimated number of affected births were, in fact, notified to the scheme.     

Prenatal screening for chromosome abnormalities using maternal serum chorionic gonadotrophin,alpha-fetoprotein,and age

Human chorionic gonadotrophin (hCG) levels were assayed retrospectively in stored maternal serum samples from 78 chromosomally abnormal pregnancies and 410 controls matched for gestation and maternal age. The median serum hCG concentration in 49 pregnancies with Down's syndrome was significantly elevated, at 2.18 multiples of the normal median. Significantly reduced hCG concentrations were found in a group of four trisomy 18 pregnancies (all less than 0.4 multiples of the median). Eight cases of unbalanced chromosome rearrangements appeared to show some lowering of hCG levels, while there was no significant difference in the levels in the cases of trisomy 13, balanced translocations, and sex chromosome abnormalities. Maternal serum hCG alone is a better indicator of Down's syndrome pregnancies than maternal age or maternal serum alpha-fetoprotein (AFP), either individually or in combination, and provides a further virtually independent measure of risk. On the basis of our findings, screening for Down's syndrome using hCG and AFP results combined with maternal age risks is predicted to result in a higher detection rate (57 per cent) for a lower false-positive rate (5.0 per cent) than would be attainable by combined AFP and age screening (37 per cent detection at a 6.6 per cent false-positive rate).     

Prenatal diagnosis of thrombocytopenia absent radius syndrome using ultrasound and fetoscopy

The prenatal diagnosis of thrombocytopenia absent radius syndrome in both dizygotic twins utilizing ultrasound, radiography and fetoscopy is described.     

对虾白斑综合症杆状病毒越冬宿主的研究

实验结果表明：在冬季即将放水干枯的虾塘中，携带WSBV的厚蟹可达15％，其中在88．9％的病蟹能活至翌年春天，并引起新的白斑综合症爆发。用患白斑综合症的斑节对虾投喂厚蟹和虎头蟹，只能引起40％的死亡率。用发病虾塘的幼厚蟹投喂斑节对虾，在6d内引起死亡率达73．9％，死亡的斑节对虾具有典型的白斑综合症病征。根据研究的结果，我们认为厚蟹是WSBV的越冬宿主。     

Amniotic fluid pregnancy-specific β1-glycoprotein (SP1) in fetal developmental disorders

Concentration of pregnancy-specific β1-glycoprotein (SP1) was studied in second and third trimester amniotic fluid from pregnancies with various fetal developmental disorders. The material consisted of 26 cases with chromosomal disorders and 19 cases with nonchromosomal fetal malformations. The SP1 concentration was elevated in two cases of Meckel's syndrome (mean + 2.7–4.0 S.D.) as well as in one case of fetal triploidy (mean + 22 S.D.), while it was normal in all other 14 different fetal disorders.     

Value of maternal serum unconjugated oestriol measurement in prenatal screening for Down's syndrome

We compared the medical and financial cost-effectiveness of prenatal serum screening for Down's syndrome using maternal age, serum alpha-fetoprotein and human chorionic gonadotrophin with and without the use of unconjugated oestriol. The use of unconjugated oestriol is medically more cost-effective than screening without it at all levels of detection. The actual performance depends on whether gestational age is estimated using ‘dates’ or an ultrasound scan. At a detection rate of 60 per cent, the proportion of unaffected fetal losses per case diagnosed at amniocentesis is about 22 per cent less if gestational age is estimated using dates (time since the first day of the last menstrual period) and about 47 per cent less if it is based on an ultrasound scan examination. At this detection rate, the inclusion of unconjugated oestriol increases costs by about £2k per case diagnosed (£36k instead of £34k) if gestational age is estimated using dates, but it is no more expensive if gestational age is measured from an ultrasound scan examination (indeed, it is more cost-effective at detection rates above 60 per cent). Since there is little change in the financial cost with the inclusion of unconjugated oestriol, for the improved medical performance of screening, it is worthwhile including it in the screening test.