Efficient strategies for preimplantation genetic diagnosis of spinal muscular atrophy.

OBJECTIVE: To develop and apply efficient multiplex preimplantation genetic diagnosis (PGD) protocols for spinal muscular atrophy (SMA).
DESIGN: Two multiplex PGD protocols were developed allowing the detection of the common homozygous deletion of the telomeric spinal muscular atrophy gene (SMN1), together with two microsatellites located on each side of SMN1.
SETTING: The molecular genetics laboratory of the university hospital in Montpellier. PATIENT(S): A couple who had already given birth to a child affected with SMA. INTERVENTION(S): In vitro fertilization using intracytoplasmic sperm injection (ICSI) and blastomere biopsy. MAIN OUTCOME MEASURE(S): Improvement of PGD for SMA. RESULT(S): Two different multiplex protocols were set up on 81 (multiplex A) and 64 single cells (multiplex B) from normal controls, affected patients, and individuals with homozygous SMN2 deletion. In one PGD cycle that used one of these protocols, two embryos were transferred, which resulted in the birth of a healthy baby. CONCLUSION(S): Analysis of microsatellite markers in addition to the SMN1 deletion allows the detection of contamination, the study of ploidy of the biopsied blastomeres, and the performance of an indirect genetic diagnosis, thereby increasing the reliability of the results. This PGD assay may be applied to all families with the common deletion of SMN1 and also to couples in whom one of the partners carries a small intragenic mutation in SMN1, identified in about 6% of affected individuals who do not lack both copies of SMN1.