Pregnancy following preimplantation genetic diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Objective Presentation of a novel case, involving the design and implementation of preimplantation genetic diagnosis (PGD) for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods The disease‐causing mutation, c.459C>T (R153C) in exon 4 of the Notch3 gene, was previously identified in the affected father. The family already had a pregnancy termination following prenatal diagnosis and chose to undergo PGD. A PGD protocol was designed to include informative, linked short tandem repeat (STR) markers and an intragenic single nucleotide polymorphism (SNP), coupled to mutation identification. Biopsy was performed at day 3 and blastocysts were transferred on day 5 after fertilization. Standard prenatal diagnosis procedures were employed to confirm the PGD results. Results One blastomere was removed at day 3 from each of eight embryos. Detection of the c.459C>T Notch3 mutation, coupled to informative polymorphic markers, unambiguously identified three unaffected embryos. Blastocyst transfer resulted in a singleton pregnancy and subsequent prenatal diagnosis confirmed that the fetus was disease‐free. Conclusions Given the dominant, highly penetrant and potentially serious effects of Notch3 mutations, PGD for CADASIL may be considered and implemented as a reproductive option, following proper genetic counseling. Copyright © 2007 John Wiley & Sons, Ltd.