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).


METHODS
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.


METHODS
The molecular genetics laboratory of the university hospital in Montpellier.


METHODS
A couple who had already given birth to a child affected with SMA.


METHODS
In vitro fertilization using intracytoplasmic sperm injection (ICSI) and blastomere biopsy.


METHODS
Improvement of PGD for SMA.


RESULTS
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.


CONCLUSIONS
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.
Girardet
Anne
A
Laboratoire de Génétique Moléculaire, Université Montpellier 1, UFR de Médecine, Inserm, U827, CHU Montpellier, Institut Universitaire de Recherche Clinique (IURC), Montpellier, France. anne.girardet@montp.inserm.fr
Fernandez
Céline
C
Claustres
Mireille
M
D000328:Adult; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D019836:Preimplantation Diagnosis / Q000379:methods*; D016601:RNA-Binding Proteins / Q000235:genetics; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein