Prenatal diagnosis of Pelizaeus-Merzbacher disease: detection of proteolipid protein gene duplication by quantitative fluorescent multiplex PCR

A prenatal diagnosis of Pelizaeus-Merzbacher disease (PMD) resulting from proteolipid protein gene (PLP) duplication was performed by a quantitative fluorescent multiplex PCR method. PLP gene copy number was determined in the proband, the pregnant mother, the male fetus and two aunts. Small amounts of genomic DNA extracted from peripheral blood and from chorionic villi were used. The fetus, in common with the proband, was identified as PMD-affected being a carrier of the PLP gene duplication, inherited from the mother, while the two aunts were non-carriers. The data obtained were confirmed by segregation analysis of a PLP-associated dinucleotide-repeat polymorphism amplified by the same multiplex PCR. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis of friedreich ataxia: Improved accuracy by using new genetic flanking markers

Friedreich ataxia is a neurodegerative disorder with autosomal recessive inheritance. Since the gene causing mutation has not yet been identified, prenatal, predictive, and carrier diagnoses are based on indirect haplotype analysis with closely linked markers. Until recently, only distal markers were available and their physical distance to the Friedreich ataxia (FRDA) gene remained elusive. The identification of close flanking markers that mark out the boundaries of the FRDA locus and reduce the critical genomic region which contains the gene allows for the first time misdiagnosis due to undetectable recombination to be avoided and diagnosis accuracy to be greatly improved. In this sense, we have verified a prenatal diagnosis in which the fetus was diagnosed as an unaffected carrier last year with a confidence of 95 per cent. By using the new flanking markers, the diagnosis improved and confidence reached almost 100 per cent.     

Prenatal diagnosis using interphase fluorescence in situ hybridization (FISH): 2-year multi-center retrospective study and review of the literature

Since 1993, the position of the American College of Medical Genetics (ACMG) has been that prenatal interphase fluorescence in situ hybridization (FISH) is investigational. In 1997, the FDA cleared the AneuVysion^® assay (Vysis, Inc.) to enumerate chromosomes 13, 18, 21, X and Y for prenatal diagnosis. Data is presented from the clinical trial that led to regulatory clearance (1379 pregnancies) and from retrospective case review on 5197 new pregnancies. These studies demonstrated an extremely high concordance rate between FISH and standard cytogenetics (99.8%) for specific abnormalities that the AneuVysion assay is designed to detect. In 29 039 informative testing events (6576 new and 22 463 cases in the literature) only one false positive (false positive rate=0.003%) and seven false negative results (false negative rate=0.024%) occurred. A historical review of all known accounts of specimens tested is presented (29 039 using AneuVysion and 18 275 specimens tested with other probes). These performance characteristics support a prenatal management strategy that includes utilization of FISH for prenatal testing when a diagnosis of aneuploidy of chromosome 13, 18, 21, X or Y is highly suspected by virtue of maternal age, positive maternal serum biochemical screening or abnormal ultrasound findings. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis of sex chromosome aneuploidy: possible reasons for high rates of pregnancy termination

Sex chromosome aneuploidy (SCA), when detected in amniocentesis, is usually an unexpected result of a test carried out for another purpose. For most SCAs, the prognosis is milder and less predictable than trisomy 21, and therefore parents are faced with a difficult decision regarding the option of pregnancy termination. While studies from Europe and the USA report a declining trend in termination rates for SCA, our local experience is different. During the period 1989–1998, we diagnosed 60 SCA (including mosaics) in 20 106 amniocenteses (0.29%) and 48 (80%) of these pregnancies were terminated, a significantly higher proportion than has been reported in Europe and the USA. The present study shows that the difference between our experience and others' may be related to differences in cultural norms and values. Thirty women were interviewed, of whom 23 terminated and seven continued the pregnancy. Interview analyses showed that the main reason behind the decision to terminate the pregnancy was associated with the parents' fear of non-specific abnormality of the child, and concerns about abnormal sexual development. Although genetic counseling practised in our center aims to be non-directive, 56% of the women reported that the counseling was either directive towards termination, or that they at least felt that the counselor's attitude was pro-termination. Most women (93%) reported themselves as having come to terms with their decision. Copyright © 2001 John Wiley & Sons, Ltd.