Reliability of preimplantation diagnosis for single gene disorders

Reliability of preimplantation genetic diagnosis (PGD) depends on controlli ng one of the most important limitations of single cell PCR, undetected all ele drop out (ADO), which may lead to misdiagnosis. To avoid this we introd uced mutation analysis simultaneously with linked polymorphic markers, pre- selecting only those embryos whose unaffected status could be confirmed by at least one linked polymorphic marker. We applied this strategy for testin g 1047 oocytes, from which 237 unaffected ones were pre-selected for transf er back to patients, resulting in 34 unaffected pregnancies and birth of 23 healthy children. Embryos originating from mutant oocytes and those with i nsufficient marker information were followed up by multiplex PCR to confirm single cell PCR diagnosis. Of 75 (85%) detected ADO, only seven (under 1%) were missed in the actual PGD, demonstrating high reliability of PGD (98%) based on multiplex single cell PCR. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.