Boronat S, Shaaya E A, Doherty C M, Caruso P, Thiele E A
Department of Neurology, Herscot Center for TSC, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatric Neurology, Vall d' Hebron Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Clin Genet. 2014 Aug;86(2):149-54. doi: 10.1111/cge.12245. Epub 2013 Aug 27.
Tuberous sclerosis complex (TSC) is caused by a mutation in the TSC1 or TSC2 genes. However, 15% of patients have no mutation identified. Tubers and subependymal nodules (SENs) are the typical brain lesions in TSC and are present in 90-95% of patients. The objective of this study is to characterize the specific genotype-phenotype of patients without these lesions. We analyzed the features of 11 patients without typical TSC neuroanatomic features. Ten had TSC1/TSC2 mutational analysis, which was negative. Clinically they had lesions thought to be of neural crest (NC) origin, such as hypomelanotic macules, facial angiofibromas, cardiac rhabdomyomas, angiomyolipomas, and lymphangioleiomyomatosis. We hypothesize that patients without tubers and SENs reflect mosaicism caused by a mutation in TSC1 or TSC2 in a NC cell during embryonic development. This may explain the negative results in TSC1 and TSC2 testing in DNA from peripheral leukocytes.
结节性硬化症（TSC）由TSC1或TSC2基因的突变引起。然而，15%的患者未发现突变。结节和室管膜下结节（SENs）是TSC典型的脑部病变，90 - 95%的患者存在此类病变。本研究的目的是描述无这些病变患者的特定基因型 - 表型。我们分析了11例无典型TSC神经解剖特征患者的特征。其中10例进行了TSC1/TSC2突变分析，结果为阴性。临床上，他们有被认为起源于神经嵴（NC）的病变，如色素减退斑、面部血管纤维瘤、心脏横纹肌瘤、血管平滑肌脂肪瘤和淋巴管平滑肌瘤病。我们推测，无结节和SENs的患者反映了胚胎发育期间NC细胞中TSC1或TSC2突变导致的嵌合现象。这可能解释了外周血白细胞DNA中TSC1和TSC2检测的阴性结果。
