Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Eur J Hum Genet. 2011 Sep;19(9):1009-12. doi: 10.1038/ejhg.2011.60. Epub 2011 Apr 13.
'Apparent non-penetrance' occurs in several genetic disorders, including tuberous sclerosis complex and neurofibromatosis type 1: clinically unaffected parents may have multiple affected offspring. Germ line or somatic mosaicism in one of the parents of the index patient is the probable cause and results in an enhanced recurrence risk. Therefore, it is of great importance to use the most sensitive technology for testing DNA of the parents of the index patient for the presence/absence of the familial mutation. To detect large rearrangements multiplex ligation-depending probe amplification (MLPA) is often used. Here we show that MLPA is less sensitive in detecting low-grade somatic mosaicism than fluorescence in situ hybridization (FISH) or a mutation-specific PCR test. Therefore, we recommend FISH (if possible) or PCR analysis for the analysis of parental DNA.
“明显的外显不全”发生在几种遗传疾病中，包括结节性硬化症和 1 型神经纤维瘤病：临床未受影响的父母可能有多个受影响的后代。先证者父母之一的种系或体细 胞镶嵌现象是可能的原因，并导致复发风险增加。因此，使用最敏感的技术检测先证者父母的 DNA 中是否存在家族突变非常重要。通常使用多重连接依赖探针扩增 (MLPA) 来检测大片段重排。我们在这里表明，MLPA 在检测低级别体细 胞镶嵌方面的敏感性低于荧光原位杂交 (FISH) 或突变特异性 PCR 检测。因此，我们建议使用 FISH（如果可能）或 PCR 分析来分析父母的 DNA。
