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

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. Copyright (C) 2009 John Wiley & Sons, Ltd.