Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy
Department of Genetics, University of Parma, Parma, Italy.
Anticancer Res. 2014 Jun;34(6):3021-30.
BACKGROUND/AIM: Von Recklinghausen disease is a syndrome characterized by a wide phenotypic variability giving rise to both, cutaneous and visceral benign and malignant neoplasms. The first include cutaneous neurofibromas, subcutaneous and plexiform neurofibromas. The latter can undergo malignant transformation and/or determine elephantiasis neuromatosa. Visceral tumors may include malignant peripheral nerve sheet tumors, gastrointestinal stromal tumors, cerebral gliomas and abdominal neurofibromas. In the present study, the authors discuss the clinical and biomolecular characterization of a cohort of 20 families with a diagnosis of type 1 neurofibromatosis.
Clinically, the cohort includes three probands with elephantiasis neuromatosa and a peculiarly high incidence of breast and gastrointestinal cancer.
Among the 14 NF1 mutations documented, 10 encoding for a truncated protein have been associated to particularly aggressive clinical phenotypes including elephantiasis neuromatosa, malignant peripheral nerve sheet tumors, breast cancer, gastrointestinal stromal tumors.
This effect on protein synthesis, rather than the type of NF1 mutation, is the key to the explanation of the genotype-phenotype correlations in the context of neurofibromatosis type 1.
背景/目的：冯·雷克林豪森病是一种综合征，其特征是表型广泛多变，导致皮肤和内脏良性和恶性肿瘤。前者包括皮肤神经纤维瘤、皮下和丛状神经纤维瘤。后者可发生恶性转化和/或导致神经纤维瘤性象皮病。内脏肿瘤可能包括恶性周围神经鞘瘤、胃肠道间质瘤、脑胶质瘤和腹部神经纤维瘤。在本研究中，作者讨论了一组 20 个诊断为 1 型神经纤维瘤病的家族的临床和生物分子特征。
临床上，该队列包括 3 名患有神经纤维瘤性象皮病的先证者和乳腺癌和胃肠道癌发病率特别高的患者。
在记录的 14 个 NF1 突变中，有 10 个编码截断蛋白与特别侵袭性的临床表型相关，包括神经纤维瘤性象皮病、恶性周围神经鞘瘤、乳腺癌、胃肠道间质瘤。
这种对蛋白质合成的影响，而不是 NF1 突变的类型，是解释 1 型神经纤维瘤病中基因型-表型相关性的关键。
