title: Six unaffected livebirths following preimplantation diagnosis for spinal muscular atrophy.
abstract: Spinal muscular atrophy (SMA) is a severe neurodegenerative autosomal recessive disorder, second only in frequency to cystic fibrosis. In its most severe 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 of the telomeric copy of the SMN gene (SMN1) on chromosome 5. We have developed a novel means of preimplantation diagnosis of SMA using a nested polymerase chain reaction (PCR) amplification of exon 7 of SMN, followed by a HinfI restriction digest of the PCR product enabling the important SMN1 gene to be distinguished from the centromeric SMN2 gene which has no clinical phenotype. This method was designed to reduce the likelihood of misdiagnosis. Five couples were treated using this method. Four proceeded to embryo transfer which resulted in six liveborns (one singleton, one twin and one triplet), all free of SMA. Embryo transfer was not performed in one cycle because of PCR contamination.
authors.affiliation: Guy's and St Thomas' Centre for Preimplantation Genetic Diagnosis, Guy's, King's and St Thomas' School of Medicine, Guy's and St Thomas' Hospital, London SE1 7EH, UK. pgd@kcl.ac.uk
authors.forename: G
authors.initials: G
authors.lastname: Daniels
authors.forename: R
authors.initials: R
authors.lastname: Pettigrew
authors.forename: A
authors.initials: A
authors.lastname: Thornhill
authors.forename: S
authors.initials: S
authors.lastname: Abbs
authors.forename: A
authors.initials: A
authors.lastname: Lashwood
authors.forename: F
authors.initials: F
authors.lastname: O'Mahony
authors.forename: C
authors.initials: C
authors.lastname: Mathew
authors.forename: A
authors.initials: A
authors.lastname: Handyside
authors.forename: P
authors.initials: P
authors.lastname: Braude
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D011247:Pregnancy; D011256:Pregnancy Outcome; D019836:Preimplantation Diagnosis / Q000379:methods*; D027724:Reproductive Techniques, Assisted