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.
Eur J Hum Genet. 2010 Apr;18(4):505-8. doi: 10.1038/ejhg.2009.198. Epub 2009 Nov 11.
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.
通过检测存活运动神经元 1 基因（SMN1）的纯合缺失，脊髓性肌萎缩症的产前和胚胎植入前基因诊断（PGD）已成为可行且广泛应用的方法。新发重排导致 SMN1 基因缺失的发现，将复发风险从 25%降低到更低的百分比，残留风险来自于新发的重复突变或种系嵌合体。一对因第一个孩子患有 SMA 而被转介到我们 PGD 中心的夫妇，发现男性伴侣携带两个 SMN1 拷贝。对 12 个单个精子进行 SMN1 基因和两个侧翼标记物的分析，以确定父亲是否在一条染色体上携带 SMN1 基因的 CIS 重复，是携带者，还是缺失是新发的。我们表明，所有携带“风险单倍型”的精子都缺失了 SMN1 基因，证实了父亲的携带者身份。我们提供了一种使用基因及其连锁标记物的共同扩增来研究隐性疾病的单个生殖细胞研究的原始应用。当无法获得其他家庭成员的样本时，这种高效且简单的程序可能有助于阐明复杂的遗传情况。
