A rapid and sensitive prenatal diagnosis of familial amyloidotic polyneuropathy ATTR Val30Met by mass spectrometry

Prenat Diagn. 2009 Oct;29(10):930-3. doi: 10.1002/pd.2169.

Abstract

Objective: To make a prenatal diagnosis of familial amyloidotic polyneuropathy (FAP) by mass spectrometry with the amniotic fluid.

Methods: Amniotic-fluid samples of three non-FAP pregnant women and six amniotic-fluid samples of fetal mice whose mother was a heterozygotic FAP amyloidgenic transthyretin (ATTR) Val30Met gene carrier were collected. Electro spray ionization mass spectrometry (ESI-MS) was employed to identify and quantitatively measure the molecular weight of the human transthyretin (TTR) in the amniotic fluid.

Results: TTR was detected in the amniotic fluid of all the human samples. In four of the six fetuses of the transgenic mice, human TTR Val30Met was detected. The other two samples showed only mouse TTR without human TTR Val30Met. DNA analysis revealed that the four fetuses were TTR Val30Met positive, but two were negative. The data from the DNA analysis and ESI-MS showed a 100% concordance.

Conclusion: Mass spectrometry analysis of the amniotic fluid might be a useful tool to make a prenatal diagnosis of FAP ATTR Val30Met.

Publication types

  • Evaluation Study

MeSH terms

  • Amniotic Fluid / chemistry
  • Amyloid Neuropathies, Familial / diagnosis*
  • Amyloid Neuropathies, Familial / genetics
  • Animals
  • Antibodies / analysis
  • Antibodies / metabolism
  • DNA Mutational Analysis / methods
  • Female
  • Humans
  • Mass Spectrometry / methods*
  • Methionine / chemistry
  • Methionine / genetics
  • Mice
  • Mice, Transgenic
  • Prealbumin / analysis*
  • Prealbumin / genetics
  • Prealbumin / immunology
  • Prealbumin / metabolism
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Sensitivity and Specificity
  • Time Factors
  • Valine / chemistry
  • Valine / genetics

Substances

  • Antibodies
  • Prealbumin
  • Methionine
  • Valine