We coincidently detected an atypical deletion of at least 1.3‐Mb, encompassing the NF1 tumor suppressor gene and several adjacent genes at an apparent heterozygous level in the blood of a 65‐year‐old female patient. She had multiple subcutaneous tumors that appeared with a certain similarity of subcutaneous neurofibromas, which, however, was revealed as lipomas by histological examination. Comprehensive and exhaustive clinical and radiological examinations did not detect any neurofibromatosis type 1‐related clinical symptoms in the patient. Multiplex ligation‐dependent probe amplification detected no or only very low level of the 1.3‐Mb NF1 deletion in six lipomas and two skin biopsies. Digital polymerase chain reaction estimated the proportion of cells carrying a heterozygous NF1 deletion at 87% in the blood, and 8%, 10%, 13%, 17%, and 20%, respectively, in the five lipomas investigated by this method, confirming our hypothesis of mosaicism. Our findings suggest that de novo cases of genetic disease are potentially mosaic regardless of finding the mutation at an apparently heterozygous level in the blood and that the possibility of mosaicism should be considered in genotype–phenotype studies and genetic counseling.

中文翻译：

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由于镶嵌现象，杂合非典型 NF1 缺失的携带者中 1 型神经纤维瘤病的空表型。

我们在一名 65 岁女性患者的血液中偶然检测到至少 1.3 Mb 的非典型缺失，包括NF1肿瘤抑制基因和几个明显杂合水平的相邻基因。她有多个皮下肿瘤，与皮下神经纤维瘤有一定的相似性，但组织学检查显示为脂肪瘤。全面而详尽的临床和放射学检查未在患者中检测到任何与 1 型神经纤维瘤病相关的临床症状。多重连接依赖性探针扩增在六个脂肪瘤和两个皮肤活检中未检测到或仅检测到非常低水平的 1.3-Mb NF1缺失。数字聚合酶链反应估计携带杂合子的细胞比例在通过这种方法研究的五个脂肪瘤中，血液中 87% 的NF1缺失以及 8%、10%、13%、17% 和 20% 的NF1缺失，证实了我们的镶嵌假设。我们的研究结果表明，无论在血液中发现明显杂合水平的突变，新发遗传病病例都可能存在嵌合体，并且在基因型-表型研究和遗传咨询中应考虑嵌合体的可能性。