Recurrence risk due to germ line mosaicism: Duchenne and Becker muscular dystrophy
Recurrence risk due to germ line mosaicism: Duchenne and Becker muscular dystrophy
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DOI：
10.1111/j.1399-0004.2009.01173.x
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发表时间：
2009-05-01
影响因子：
3.5
通讯作者：
Bakker, E.
中科院分区：
文献类型：
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作者：
Helderman-van den Enden, A. T. J. M.;de Jong, R.;Bakker, E.
Helderman-van den Enden ATJM，de Jong R，den Dunnen JT，Houwing-Duistermaat JJ，Kneppers ALJ，Ginjaar HB，Breuning MH，Bakker E.生殖系嵌合体导致的复发风险：Duchenne和Becker肌营养不良症。临床遗传学2009：75：465-472。(C)Blackwell Munksgaard，2009来自明显非携带者父母的多个受影响后代的存在是由生殖系嵌合体引起的。虽然生殖系嵌合现象已被报道用于许多疾病，但只有少数疾病的复发风险数字是已知的。在X连锁杜氏和贝克肌营养不良症（DMD/BMD）中，如果风险单倍型被传播，由于生殖系嵌合体，非携带者女性的复发风险估计在14%和20%之间（95%置信区间3-30）。在这项研究中，我们分析了318例DMD/BMD病例，其中检测到的突变是从头获得一个更好的估计的“真实”的生殖系嵌合体的数量和更精确的复发风险的目的。这些知识对遗传咨询至关重要。我们的数据表明，如果风险单倍型被传递，则复发风险为8.6%（4.8-12.2），但近端（15.6%）（4.1-27.0）和远端（6.4%）（2.1-10.6）缺失之间存在显著差异。总的来说，大多数突变起源于女性。缺失更常发生在外祖母的X染色体上，而点突变发生在外祖父的X染色体上。在未单倍型的新发DMD/BMD家族中，突变复发的风险为4.3%。
Helderman-van den Enden ATJM, de Jong R, den Dunnen JT, Houwing-Duistermaat JJ, Kneppers ALJ, Ginjaar HB, Breuning MH, Bakker E. Recurrence risk due to germ line mosaicism: Duchenne and Becker muscular dystrophy.Clin Genet 2009: 75: 465-472. (C) Blackwell Munksgaard, 2009The presence of multiple affected offspring from apparently non-carrier parents is caused by germ line mosaicism. Although germ line mosaicism has been reported for many diseases, figures for recurrence risks are known for only a few of them. In X-linked Duchenne and Becker muscular dystrophies (DMD/BMD), the recurrence risk for non-carrier females due to germ line mosaicism has been estimated to be between 14% and 20% (95% confidence interval 3-30) if the risk haplotype is transmitted. In this study, we have analyzed 318 DMD/BMD cases in which the detected mutation was de novo with the aim of obtaining a better estimate of the 'true' number of germ line mosaics and a more precise recurrence risk. This knowledge is essential for genetic counseling. Our data indicate a recurrence risk of 8.6% (4.8-12.2) if the risk haplotype is transmitted, but there is a remarkable difference between proximal (15.6%) (4.1-27.0) and distal (6.4%) (2.1-10.6) deletions. Overall, most mutations originated in the female. Deletions occur more often on the X chromosome of the maternal grandmother, whereas point mutations occur on the X chromosome of the maternal grandfather. In unhaplotyped de novo DMD/BMD families, the risk of recurrence of the mutation is 4.3%.