title: Single-sperm analysis for recurrence risk assessment of spinal muscular atrophy.
abstract: With the detection of a homozygous deletion of the survival motor neuron 1 gene (SMN1), prenatal and preimplantation genetic diagnosis (PGD) for spinal muscular atrophy has become feasible and widely applied. The finding of a de novo rearrangement, resulting in the loss of the SMN1 gene, reduces the recurrence risk from 25% to a lower percentage, the residual risk arising from recurrent de novo mutation or germline mosaicism. In a couple referred to our PGD center because their first child was affected with SMA, the male partner was shown to carry two SMN1 copies. An analysis of the SMN1 gene and two flanking markers was performed on 12 single spermatozoa, to determine whether the father carried a CIS duplication of the SMN1 gene on one chromosome and was a carrier, or if the deletion has occurred de novo. We showed that all spermatozoa that were carriers of the 'at-risk haplotype' were deleted for the SMN1 gene, confirming the carrier status of the father. We provide an original application of single germ cell studies to recessive disorders using coamplification of the gene and its linked markers. This efficient and easy procedure might be useful to elucidate complex genetic situations when samples from other family members are not available.
authors.affiliation: Unité INSERM U781 Institut de Recherche Necker-Enfants Malades, service de génétique médicale, Hôpital Necker-Enfants Malades (Assistance Publique-Hôpitaux de Paris), Université Paris-Descartes, 75743 Paris Cedex 15, France. philippe.burlet@inserm.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Burlet
authors.forename: Nadine
authors.initials: N
authors.lastname: Gigarel
authors.forename: Maryse
authors.initials: M
authors.lastname: Magen
authors.forename: Séverine
authors.initials: S
authors.lastname: Drunat
authors.forename: Alexandra
authors.initials: A
authors.lastname: Benachi
authors.forename: Laetitia
authors.initials: L
authors.lastname: Hesters
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bonnefont
authors.forename: Julie
authors.initials: J
authors.lastname: Steffann
mesh_terms: D002648:Child; D005260:Female; D005820:Genetic Testing; D006720:Homozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012008:Recurrence; D018570:Risk Assessment; D013094:Spermatozoa / Q000737:chemistry*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics
chemical_list: C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein