The significance of early second-trimester sonographic detection of minor fetal renal anomalies

A study of 6350 consecutive transvaginal ultrasound examinations was performed as part of a routine fetal evaluation. Twenty-one cases (0.33 per cent) of early second-trimester sonographic detection of minor renal abnormalities (unilateral renal agenesis, pelvic kidney, and double collecting system) are presented. The sonographic diagnosis was made at 14–18 weeks of pregnancy and confirmed, in all of the 21 fetuses, postnatally or by post-mortem. A high incidence of associated fetal anomalies (24 per cent) and parental renal abnormalities (14 per cent) was demonstrated. Transvaginal sonography was found to be a useful tool for diagnosing these renal anomalies as early as 14 weeks of pregnancy. The likelihood of various associated anomalies and long-term implications on renal function raise questions concerning the prenatal management of such patients.     

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.     

A cost-benefit analysis of a population screening programme for neural tube defects

Population screening for neural tube defects is possible by measuring maternal serum alpha-fetoprotein levels with appropriate follow-up as required. British Columbia has approximately 39 000 births annually and the incidence of neural tube defects is 1–55 per 1000 births (0–94 per 1000 livebirths). Results from a cost-benefit analysis suggest that the outlined screening programme would be cost-beneficial for British Columbia. Other important factors essential to consider before instituting a population screening programme are discussed.     

Prenatal diagnosis of adult polycystic kidney disease with DNA markers on chromosome 16 and the genetic heterogeneity problem

A prenatal diagnosis of adult polycystic kidney disease by DNA testing is reported. Evidence showing a linkage between the disease and the 3′HVR and 24.1 restriction fragment length polymorphisms (RFLPs) on chromosome 16 was obtained in the proband's family by linkage analysis of data and homogeneity testing with Italian families of the linked type. Fetal genotype prediction based on both flanking markers was confirmed by histological and ultrastructural findings in fetal kidneys.     

Extra embryonic/fetal karyotypic discordance during diagnostic chorionic villus sampling

From a total of 1312 diagnostic chorionic villus samplings (CVS) there were 22 which showed discordance between the karyotype of the chorionic villi and that of the fetus. This frequency was some 20-fold higher than that reported at amniocentesis. In the majority of discordant cases, the fetal karyotype was normal while the placenta! karyotype was mosaic. In four cases, the placenta! karyotype was non-mosaic (a trisomy 16, a monosomy X, and two tetraploids) while the fetal karyotype was normal. In one case, the placenta was trisomy 18 while the fetus was mosaic. There were two ‘false-negative’ results where short-term methods showed only normal cells while both long-term cultures of chorionic villi and fetal cells were mosaic, in one 46,XY/47.XXY and in the other 46,X Y/47.X Y, + 21.     

Ontogeny of fetal liver glucose-6-phosphatase activity

A reliable and sensitive microassay for the measurement of liver glucose-6-phosphatase is described. Human fetal liver was assayed for glucose-6-phosphatase activity from 7.5 to 24 weeks of gestation and was found to have a mean activity of 2.11 nmol per min per mg of protein. This was approximately 30 per cent of the postnatal controls assayed by the same method, but there was no evidence of a change in activity during the gestational period examined. If fetal liver tissue can be reliably obtained, it may be possible to determine a deficiency of glucose-6-phosphatase in fetuses who are at risk.     

Normal pregnancy after preimplantation DNA diagnosis of a dystrophin gene deletion

To perform preimplantation DNA diagnosis for Duchenne muscular dystrophy (DMD) in a female carrier of a dystrophin gene deletion of exons 3–18, we developed a polymerase chain reaction (PCR)-based assay of exon 17 sequences. Exon 17 was efficiently amplified in all 50 single blastomeres of normal control embryos and in five blastomeres of one male embryo of the DMD carrier obtained after a first preimplantation diagnosis (PID) for gender determination. In ten blastomeres of another two male embryos of the DMD carrier, no PCR signals were observed, probably as a result of the deletion. After intracytoplasmic sperm injection, embryos were analysed for exon 17 and three of the four embryos showing normal PCR signals were replaced, resulting in a singleton pregnancy. Prenatal diagnosis showed a female karyotype and DNA analysis indicated that the fetus was not a DMD carrier.