科研之友
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摘要
Purpose: Prenatal diagnosis of fetal Mendelian disorders can benefit from noninvasive approaches using fetal cell-free DNA in naternal plasma. Detecting metabolic disorders before birth can result in immediate treatment postpartum in order to optimize outcome. %26lt;br%26gt;Methods: We developed a mathematical model-and at experimental methodology to analyze the case of a fetus with a 25% risk of inheriting two known mutations in MUT that cause methylmalonic acidemia. To accomplish this, we measured allelic counts at the mutation sites and the fetal fraction from high minor-allele-frequency single:nucleotide polymorphism positions. %26lt;br%26gt;Results: By counting linked alleles, the test was able to distinguish 11 positive markers from the negative controls and thereby determine whether or not the mutations carried by the parents were inherited, by the fetus. For a homozygous fetus, the Z-score of the mutation site was 5.97, whereas the median Z-score of-all the linked alleles was 4.56 when all negative (heterozygous) controls had a Z-score %26lt;2.5. %26lt;br%26gt;Conclusion: The application of this methodology for diagnosing methylmalonic acidemia shows that this is a cost-effective and non-invasive approach to diagnosing known mutations related to Mendelian disorders in the fetus.
- 出版日期2014-7
