Department of Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hum Mutat. 2020 Jul;41(7):1226-1231. doi: 10.1002/humu.24022. Epub 2020 Apr 13.
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.
我们偶然在一位 65 岁女性患者的血液中检测到至少 1.3-Mb 的非典型缺失，该缺失至少包含 NF1 肿瘤抑制基因和几个相邻基因，且表现为杂合子状态。该患者有多个皮下肿瘤，其外观与皮下神经纤维瘤具有一定相似性，但组织学检查显示为脂肪瘤。全面详尽的临床和影像学检查未发现该患者存在任何 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 6 个脂肪瘤和 2 个皮肤活检中均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血液中携带杂合 NF1 缺失的细胞比例为 87%，而通过该方法检测的 5 个脂肪瘤中分别为 8%、10%、13%、17%和 20%，证实了我们的嵌合体假说。我们的研究结果表明，新发的遗传疾病可能是嵌合体，无论在血液中发现的突变是否处于明显的杂合子水平，在基因型-表型研究和遗传咨询中都应考虑嵌合体的可能性。
