Preimplantation and prenatal genetic diagnosis of aromatic L-amino aciddecarboxylase deficiency with an amplification refractory mutation system-quantitative polymerase chain reaction
Journal
Taiwanese Journal of Obstetrics and Gynecology
Journal Volume
50
Journal Issue
4
Pages
468-473
Date Issued
2011
Author(s)
Kuo S.-J.
Ma G.-C.
Chang S.-P.
Wu H.-H.
Chen C.-P.
Chang T.-M.
Lin W.-H.
Wu S.-H.
Lee M.-H.
Chen M.
Abstract
OBJECTIVES: To develop a diagnostic platform for preimplantation genetic diagnosis (PGD) and prenatal genetic diagnosis (PND) to prevent births of aromatic L-amino acid decarboxylase deficiency (AADC) patients. MATERIALS AND METHODS: Five Taiwanese families carrying AADC were enrolled. A novel technique, amplification refractory mutation system-quantitative polymerase chain reaction (ARMS-qPCR), was developed for both of PGD and PND. For PGD, blastomere biopsies of day-3 cleavage-stage embryos were subjected to ARMS-qPCR. Villi, cultured amniocytes, or both were used to confirm the PGD result; this approach could also be used as the sole method for PND after in vivo conception). RESULTS: Unaffected live births were achieved in four of the five families, except one with ongoing PGD. The ARMS-qPCR correctly classified blastomeres (from day-3 cleavage-stage embryos) as affected (homozygous mutant), carrier (heterozygous for mutant and wild-type alleles), or normal (homozygous wild-type) within 1 working day. CONCLUSIONS: To our knowledge, this is the first report of successful PGD of AADC. The molecular technique we devised (ARMS-qPCR) was applicable for PGD as well as PND of AADC. Furthermore, it has great potential for similar applications in other monogenic disorders.
Type
journal article