Six unaffected livebirths following preimplantation diagnosis for spinal muscular atrophy

Spinal muscular atrophy (SMA) is a severe neurodegenerative autosomal reces sive disorder, second only in frequency to cystic fibrosis. In its most sev ere form, SMA type I (Werdnig-Hoffman), death invariably ensues before age 2 years from respiratory failure or infection. Around 98% of clinical cases of SMA are caused by the homozygous absence of a region of exons 7 and 8 o f the telomeric copy of the SMN gene (SMN1) on chromosome 5. We have develo ped a novel means of preimplantation diagnosis of SMA using a nested polyme rase chain reaction (PCR) amplification of exon 7 of SMN, followed by a Hin fI restriction digest of the PCR product enabling the important SMN1 gene t o be distinguished from the centromeric SMN2 gene which has no clinical phe notype. This method was designed to reduce the likelihood of misdiagnosis. Five couples were treated using this method. Four proceeded to embryo trans fer which resulted in six liveborns (one singleton, one twin and one triple t), all free of SMA. Embryo transfer was not performed in one cycle because of PCR contamination.