Experiences of mothers participating in maternal serum screening for Down's syndrome.

The participation rate in a maternal serum screening for trisomy 21 was 84% in the Helsinki trial. Six hundred and twenty-five mothers who had a positive result and a random sample of 245 mothers who had a negative result took part in the opinion survey. Ninety-five percent of the first and 97% of the second group considered the screening tests as very or quite useful. However, 12% of those with a positive result would decide against taking the test if they could reconsider, whereas 100% of those with a negative result would take it again. Too little information about the test, worries and stress, unnecessary in cases of false timing, difficult decision-making, and anxiety while awaiting the results of the chromosome study were the main complaints. More information at all stages, earlier testing, ultrasound timing before the serum test, and fast results were considered essential.

Structural organization and genomic sequence of mouse syndecan-1 gene.

Syndecan-1 is an integral membrane proteoglycan, which binds several extracellular matrix components and growth factors. Its expression follows morphogenetic rather than histological patterns during embryonic development and is regulated by epithelial-mesenchymal interactions during organogenesis. Malignant transformation has been shown to suppress syndecan-1 expression. In order to understand better the regulation of syndecan-1 expression, we have determined the structural organization of mouse syndecan-1 gene. Several genomic clones were isolated, covering the entire 23-kilobase (kb) syndecan-1 gene. All five exons, four introns, and the 5'- and 3'-flanking regions were sequenced. The first intron was very long (17,582 base pairs (bp)) if compared with the others that were only a few hundred nucleotides in length. The first exon contained only the signal sequence and exons II-IV all the glycosaminoglycan binding sites. The fifth exon resided both transmembrane and cytoplasmic domains, which are known to be conserved among the members of the syndecan family. This genomic structure explains why these members could have heterologous extracellular domains and homologous transmembrane and cytoplasmic domains. Syndecan-1 gene was shown by primer extension analysis to have three transcription initiation sites which were confirmed by polymerase chain reaction. These initiation sites were found to locate -217, -266, and -591 bp from described cDNA (Saunders, S., Jalkanen, M., O'Farrell, S., and Bernfield, M. (1989) J. Cell Biol. 108, 1547-1556). Within the 5'-end of the gene a 2000-bp-long CpG nucleotide-rich sequence resembling a CpG island was found, which started from the transcription initiation sites and ended in the first intron. At the 3'-end of the gene an other polyadenylation signal sequence was revealed 638 bp downstream from the first one. The two mRNAs (2.6 kb and 3.4 kb) were shown to be produced by alternative polyadenylation.

The mapping and visual ordering of the human syndecan-1 and N-myc genes near the telomeric region of chromosome 2p.

The chromosomal locations of the human and mouse syndecan genes have been shown to associate with the corresponding locations of members of the myc gene family, proto-oncogenes that code for transcription factors. Here, we demonstrate the precise localization and order of the human syndecan-1 and N-myc genes using fluorescence in situ hybridization techniques that provide different levels of resolution. By visualizing the actual centromere-telomere orientation of these two genes, the human syndecan-1 gene is localized to 2p23-24, just centromeric to the N-myc gene at 2p24.1.

Maternal serum screening for Down's syndrome on population basis.

BACKGROUND: The favorable attitude among the public towards prenatal diagnostics in Finland allowed us to start a trial on population basis when screening for Down's syndrome by maternal serum markers and age was introduced. METHODS: Screening by maternal serum markers for Down's syndrome was offered to all 17,200 pregnant women in the Helsinki area during the study period of 2.5 years. Screening due to advanced maternal age, 37 years or more, was continued as previously, and 1133 pregnant mothers used this option. Alpha-fetoprotein, human chorionic gonadotrophin, and during the first year also unconjugated estriol were used as markers. RESULTS: The uptake of serum screening was 84%. The proportion of false positive results i.e. risk for Down's syndrome, 1:350 or more at term, was initially 5.7%. After ultrasound scan 4.1% of the mothers remained 'screen positive'. The amniocentesis or chorionic villus sampling uptake was 98.4%. Ten out of eighteen cases of Down's syndrome were detected by maternal serum screening, sensitivity 56%, 95% CI 31-79%. Other chromosomal abnormalities were found in three cases, and there were four cases of mosaicisms confined to the placenta. These were trisomies 16, 7 and 2, and tetraploidy. Elevated serum alpha-fetoprotein was found initially in 0.7% of the cases. One case of congenital nephrosis of the Finnish type and ten other, mainly structural, abnormalities were detected by high AFP. CONCLUSIONS: The screening was well received by the mothers. The detection rate of 56% is in the same range as in previous studies. Ultrasound scan before the test would effectively lower the false positive rate caused by incorrect timing.

Usefulness of chromosome 19 RFLP haplotypes in the diagnosis of myotonic dystrophy.

Three DNA probes (APOC2, PSC11, and LDR152) detecting RFLP polymorphisms were used to test the usefulness of the RFLP approach in myotonic dystrophy (MD) families from the isolated Finnish population. The informativeness of these polymorphisms did not differ from that reported in more mixed populations: in the 13 families of the study most of the 79 meiotic events studied were informative. One known recombinant is included in the study. The highest lod score obtained in the multilocus linkage analysis was z = 5.941 at recombination fraction theta = 0.02. The RFLP results significantly facilitated genetic counseling in problematic cases among the families studied. Although evidence could be found for linkage disequilibrium of the RFLP haplotypes formed in Finnish MD patients, our results do not exclude the possible existence of more than one ancient MD mutation in this population.

Linkage disequilibrium detected between dystrophia myotonica and APOC2 locus in the Finnish population.

Three polymorphic loci APOC2, CKMM and p134C were used to haplotype 15 Finnish dystrophia myotonica (DM) families representing about one third of all DM patients in this isolated population. Compound APOC2 and CKMM haplotypes reveal linkage disequilibrium: 90% of DM chromosomes co-occur with the haplotypes that occur in 31% of normal chromosomes only. The same disequilibrium is present when only polymorphisms occurring at the APOC2 locus are used. Surprisingly, no statistically significant linkage disequilibrium was discovered at the CKMM locus alone. Of the meiotic events, 84% were informative when both APO2 and CKMM loci were used. When studied selectively, 60% of meiotic events were informative at the APOC2 locus, whereas CKMM alone resulted in 65% meiotic informativeness. The distal marker p134C was found to have an unfortunately low information content in our population.