Serum screening for Down's syndrome between 8 and 14 weeks of pregnancy

Wald, Nicholas; George, Lynne M.; Smith, David H.G.; Densem, J. W.; Pettersonm, K.

doi:10.1111/j.1471-0528.1996.tb09765.x

Cited by 181 publications

(87 citation statements)

References 26 publications

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“…PAPP-A is one of four proteins originally isolated in 1974 from normal human pregnancy serum (24). Although knowledge of PAPP-A's biological function was lacking, particular interest in PAPP-A had developed with its suggested clinical utility as an index of placental function and a firsttrimester screen for Down's Syndrome (25,26). In addition, placental PAPP-A ''knock-out'' in humans appears to be associated with Cornelia de Lange syndrome, a condition involving incomplete fetal development and subsequent deformities (27).…”

Section: Resultsmentioning

confidence: 99%

The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A

Lawrence

Oxvig

Overgaard

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

648

469

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Proteolytic cleavage of the six known insulinlike growth factor binding proteins (IGFBPs) is a powerful means of rapid structure and function modification of these important growth-regulatory proteins. Intact IGFBP-4 is a potent inhibitor of IGF action in vitro, and cleavage of IG-FBP-4 has been shown to abolish its ability to inhibit IGF stimulatory effects in a variety of systems, suggesting that IGFBP-4 proteolysis acts as a positive regulator of IGF bioavailability. Here we report the isolation of an IGFdependent IGFBP-4-specific protease from human fibroblastconditioned media and its identification by mass spectrometry microsequencing as pregnancy-associated plasma protein-A (PAPP-A), a protein of unknown function found in high concentrations in the maternal circulation during pregnancy. Antibodies raised against PAPP-A both inhibited and immunodepleted IGFBP-4 protease activity in human fibroblastconditioned media. Moreover, PAPP-A purified from pregnancy sera had IGF-dependent IGFBP-4 protease activity. PAPP-A mRNA was expressed by the human fibroblasts and osteoblasts, and PAPP-A protein was secreted into the culture medium. In conclusion, we have identified an IGF-dependent IGFBP protease and at the same time assigned a function to PAPP-A. This represents an unanticipated union of two areas of research that were not linked in any way before this report.

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Section: Resultsmentioning

confidence: 99%

The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A

Lawrence

Oxvig

Overgaard

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

648

469

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“…One of these genes encodes for PAPP-A, one of the four proteins originally isolated in 1974 from normal human pregnancy serum (Lin et al, 1974). Even though the biological function of PAPP-A was unclear at that time, particular interest in PAPP-A had been generated because of its clinical utility as an index of placental function and a first-trimester screen for Down's syndrome (Stabile et al, 1988;Wald et al, 1996). Recently, PAPP-A was identified as the IGFdependent protease that cleaves the 26 kDa insulin-like growth factor binding protein-4 (IGFBP-4) into two proteolytic products (Lawrence et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the common fragile site FRA9E and its potential role in ovarian cancer

et al. 2003

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Common fragile sites (CFSs) are regions of profound genomic instability that have been hypothesized to play a role in cancer. The major aim of this study was to locate a fragile region associated with ovarian cancer. Differential display (DD)-PCR analysis comparing normal ovarian epithelial cultures and ovarian cancer cell lines identified pregnancy-associated plasma protein-A (PAPPA) because of its frequent loss of expression (LOE) in ovarian cancer cell lines. PAPPA is localized to human chromosome 9q32-33.1, a region associated with significant loss of heterozygosity (LOH) in ovarian tumors (>50%) and in close proximity to the FRA9E CFS. FISH analysis determined that PAPPA was contained within the distal end of FRA9E. Characterization of FRA9E determined that aphidicolin-induced instability extended over 9 Mb, identifying FRA9E as the largest CFS characterized to date. Comprehensive LOH analysis revealed several distinct peaks of LOH within FRA9E. Semiquantitative RT-PCR analysis of 16 genes contained within FRA9E indicated that genes showing LOE in ovarian tumors coincided with regions of high LOH. PAPPA displayed the most significant loss (72%). This study provides evidence to suggest that instability within FRA9E may play an important role in the development of ovarian cancer and lends further support for the hypothesis that CFSs may be causally related to cancer.

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“…2,6,12,13 The individual analyte values in both series are converted to MoMs and these values are then usually log 10 transformed and their distributions checked for a Gaussian ¢t, prior to calculating the log 10 mean and log 10 SD for each analyte in each series and also the correlation between each analyte in each series.…”

Section: Discussionmentioning

confidence: 99%

The effect of temporal variation in biochemical markers of trisomy 21 across the first and second trimesters of pregnancy on the estimation of individual patient-specific risks and detection rates for Down's syndrome

Spencer

Crossley²,

Aitken³

et al. 2003

Ann Clin Biochem

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Background In a previous study we examined the changes in the median multiple of the median (MoM) with gestation of free beta human chorionic gonadotrophin (FbhCG), total human chorionic gonadotrophin (ThCG), a-fetoprotein (AFP) and pregnancy-associated plasma protein A (PAPP-A) in a large series of Down's syndrome pregnancies. Results showed that there was a significant temporal variation of the MoM for each marker. In this paper, we assess the impact of this temporal shift on the estimation of patient-specific risks and the detection rates (DRs) for Down's syndrome pregnancies.

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Serum screening for Down's syndrome between 8 and 14 weeks of pregnancy

Cited by 181 publications

References 26 publications

The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A

The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A

Characterization of the common fragile site FRA9E and its potential role in ovarian cancer

The effect of temporal variation in biochemical markers of trisomy 21 across the first and second trimesters of pregnancy on the estimation of individual patient-specific risks and detection rates for Down's syndrome

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