Predictive diagnosis of familial adenomatous polyposis with linked DNA markers: population based study

F. MacDonald, D.G. Morton, P.M. Rindl, J. Haydon, R. Cullen, J. Gibson, J.P. Neoptolemos, M.R. Keighley, C.M. McKeown, M. Hultén

Research output: Contribution to journalArticle

Abstract

OBJECTIVES--To evaluate the use of polymorphic DNA probes linked to the APC gene in the presymptomatic diagnosis of familial adenomatous polyposis. DESIGN--Four DNA probes were tested on an unselected population of patients at risk of familial adenomatous polyposis. SUBJECTS--The first 47 families notified to the West Midlands familial adenomatous polyposis register. Plus five families sent to our hospital as part of the West of Britain DNA consortium. MAIN OUTCOME MEASURES--The proportion of families and family members in whom DNA testing could be used to adjust the estimate of risk. RESULTS--Only 17 families on the register (containing 46% (74/162) of the population at risk) had a suitable pedigree structure for DNA analysis. DNA was analysed in 12 of these families plus the five families from the West of Britain consortium. At least one probe was informative in 27 of the 33 subjects born with 50% risk, but the most informative probe (pi 227) was the one with the highest recombination rate (10%). Flanking markers were informative in only four of the 33 subjects. CONCLUSIONS--These findings confirm the potential for accurate predictive diagnosis of familial adenomatous polyposis with polymorphic DNA probes, but such an approach is currently limited to about one third of affected families. A combined approach to presymptomatic diagnosis, which includes DNA testing and indirect ophthalmoscopy, is advocated.
Original languageEnglish
Pages (from-to)869-872
Number of pages4
JournalBMJ
Volume304
Issue number6831
DOIs
Publication statusPublished - 4 Apr 1992

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Adenomatous Polyposis Coli
Genetic Markers
Population
DNA Probes
DNA
APC Genes
Ophthalmoscopy
Pedigree
Genetic Recombination

Keywords

  • Adenomatous Polyposis Coli
  • Adolescent
  • Adult
  • Child
  • DNA Probes
  • DNA, Neoplasm
  • Genetic Markers
  • Humans
  • Middle Aged
  • Pedigree
  • Predictive Value of Tests
  • Risk Factors

Cite this

MacDonald, F., Morton, D. G., Rindl, P. M., Haydon, J., Cullen, R., Gibson, J., ... Hultén, M. (1992). Predictive diagnosis of familial adenomatous polyposis with linked DNA markers: population based study. BMJ, 304(6831), 869-872. https://doi.org/10.1136/bmj.304.6831.869
MacDonald, F. ; Morton, D.G. ; Rindl, P.M. ; Haydon, J. ; Cullen, R. ; Gibson, J. ; Neoptolemos, J.P. ; Keighley, M.R. ; McKeown, C.M. ; Hultén, M. / Predictive diagnosis of familial adenomatous polyposis with linked DNA markers : population based study. In: BMJ. 1992 ; Vol. 304, No. 6831. pp. 869-872.
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MacDonald, F, Morton, DG, Rindl, PM, Haydon, J, Cullen, R, Gibson, J, Neoptolemos, JP, Keighley, MR, McKeown, CM & Hultén, M 1992, 'Predictive diagnosis of familial adenomatous polyposis with linked DNA markers: population based study', BMJ, vol. 304, no. 6831, pp. 869-872. https://doi.org/10.1136/bmj.304.6831.869

Predictive diagnosis of familial adenomatous polyposis with linked DNA markers : population based study. / MacDonald, F.; Morton, D.G.; Rindl, P.M.; Haydon, J.; Cullen, R.; Gibson, J.; Neoptolemos, J.P.; Keighley, M.R.; McKeown, C.M.; Hultén, M.

In: BMJ, Vol. 304, No. 6831, 04.04.1992, p. 869-872.

Research output: Contribution to journalArticle

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T1 - Predictive diagnosis of familial adenomatous polyposis with linked DNA markers

T2 - population based study

AU - MacDonald, F.

AU - Morton, D.G.

AU - Rindl, P.M.

AU - Haydon, J.

AU - Cullen, R.

AU - Gibson, J.

AU - Neoptolemos, J.P.

AU - Keighley, M.R.

AU - McKeown, C.M.

AU - Hultén, M.

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Y1 - 1992/4/4

N2 - OBJECTIVES--To evaluate the use of polymorphic DNA probes linked to the APC gene in the presymptomatic diagnosis of familial adenomatous polyposis. DESIGN--Four DNA probes were tested on an unselected population of patients at risk of familial adenomatous polyposis. SUBJECTS--The first 47 families notified to the West Midlands familial adenomatous polyposis register. Plus five families sent to our hospital as part of the West of Britain DNA consortium. MAIN OUTCOME MEASURES--The proportion of families and family members in whom DNA testing could be used to adjust the estimate of risk. RESULTS--Only 17 families on the register (containing 46% (74/162) of the population at risk) had a suitable pedigree structure for DNA analysis. DNA was analysed in 12 of these families plus the five families from the West of Britain consortium. At least one probe was informative in 27 of the 33 subjects born with 50% risk, but the most informative probe (pi 227) was the one with the highest recombination rate (10%). Flanking markers were informative in only four of the 33 subjects. CONCLUSIONS--These findings confirm the potential for accurate predictive diagnosis of familial adenomatous polyposis with polymorphic DNA probes, but such an approach is currently limited to about one third of affected families. A combined approach to presymptomatic diagnosis, which includes DNA testing and indirect ophthalmoscopy, is advocated.

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KW - Child

KW - DNA Probes

KW - DNA, Neoplasm

KW - Genetic Markers

KW - Humans

KW - Middle Aged

KW - Pedigree

KW - Predictive Value of Tests

KW - Risk Factors

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MacDonald F, Morton DG, Rindl PM, Haydon J, Cullen R, Gibson J et al. Predictive diagnosis of familial adenomatous polyposis with linked DNA markers: population based study. BMJ. 1992 Apr 4;304(6831):869-872. https://doi.org/10.1136/bmj.304.6831.869