ON THE ORIGIN OF DELETIONS AND POINT MUTATIONS IN DUCHENNE MUSCULAR-DYSTROPHY - MOST DELETIONS ARISE IN OOGENESIS AND MOST POINT MUTATIONS RESULT FROM EVENTS IN SPERMATOGENESIS
ON THE ORIGIN OF DELETIONS AND POINT MUTATIONS IN DUCHENNE MUSCULAR-DYSTROPHY - MOST DELETIONS ARISE IN OOGENESIS AND MOST POINT MUTATIONS RESULT FROM EVENTS IN SPERMATOGENESIS
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DOI：
10.1136/jmg.31.3.183
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发表时间：
1994-03-01
影响因子：
4
通讯作者：
MULLER, B
中科院分区：
文献类型：
--
作者：
GRIMM, T;MENG, G;MULLER, B
我们目前的研究结果的突变率和起源的杜氏肌营养不良症（DMD）。根据患者中存在的突变类型（缺失/重复或点突变），男性与女性的突变率比例存在很大差异。在缺失突变中，男性突变率仅为女性的30%。在非缺失/非重复突变（可能含有高比例的点突变）中，男性突变率至少是女性突变率的2.2倍，甚至可能更高。考虑到常染色体隐性表型的存在，我们发现非缺失/非重复突变的k值为40.3。这些结果表明，绝大多数缺失发生在卵子发生过程中，而大多数点突变起源于精子发生过程。以前的研究表明，在其他疾病和基因中，最明显的是血友病B和A，还有ZFY和ZFX基因，男性的点突变率往往高于女性。我们的研究结果可以被看作是对DMD这一特殊情况的确认。对风险数字的影响是相当大的。作为一个例子，一个孤立的DMD病例的母亲没有明显的基因结构异常的风险增加到至少76%的载体。考虑到上述常染色体隐性表型的存在，k的估计值为40.3，它甚至进一步增加到98%。然而，由于置信区间仍然很大，需要更多的数据来改进估计数。在此背景下讨论了Germinal mosaicism。
We present the results of a study of the rate and origin of mutations in Duchenne muscular dystrophy (DMD). Depending on the type of mutation (deletion/duplication or point mutation) present in the patient, there are widely varying ratios of male to female mutation rates. In deletions, the male mutation rate is only 30% of the female one. In non-deletional/non-duplicational mutations (presumably containing a high proportion of point mutations) the male mutation rate is at least 2.2 as high as the female one and probably much higher. Allowing for the presence of autosomal recessive phenocopies we find that k in non-deletional/non-duplicational mutations is 40.3.These findings mean that the vast majority of deletions arise in oogenesis, while most point mutations stem from spermatogenesis. Previous investigations have shown that in other diseases and genes, most notably haemophilia B and A, but also the ZFY and ZFX genes, the male mutation rate for point mutations tends to be higher than the female one. Our results can be seen as a confirmation of this for the special case of DMD.The influence on risk figures is considerable. As an example, the risk of the mother of an isolated case of DMD without an apparent structural anomaly of the gene of being a carrier increases from 67% to at least 76%. Given the estimate of 40.3 for k, allowing for the presence of autosomal recessive phenocopies mentioned above, it increases even further to 98%. However, as confidence intervals are still large, more data are needed to improve the estimates. Germinal mosaicism in this context is discussed.