PDF(Pubmed)
Abstract：
Schwannomatosis (SWN) is a rare genetic condition characterized by the risk of developing multiple benign peripheral nerve sheath tumors; however, the risk of developing malignant tumors in patients with SWN remains unclear. This study described the case of a 57-year-old Japanese man diagnosed with SWN whose older brother also had SWN. Whole-exome sequencing identified a heterozygous mutation [c.1018C > T (p.Arg340X)] in the LZTR1 gene, linked to the RAS/MAPK pathway, in the patient and his brother. Moreover, the patient had aphasia and right-sided paralysis because of a brain tumor. RNA sequencing revealed the remarkable upregulation of several genes associated with oxidative stress, such as the reactive oxygen species pathway and oxidative phosphorylation, a downstream effector of the RAS/MAPK pathway, in the the patient and his brother compared with healthy volunteers. The final diagnosis was LZTR1-related familial SWN, and the dysregulated RAS/MAPK pathway in this patient might be associated with brain tumorigenesis.
摘要：
神经鞘瘤病（SWN）是一种罕见的遗传病，其特征是发生多发性良性周围神经鞘瘤的风险；然而，SWN患者发生恶性肿瘤的风险尚不清楚.这项研究描述了一名57岁的日本男子被诊断患有SWN，其哥哥也患有SWN。全外显子组测序鉴定出杂合突变[c.1018C>T（p。Arg340X）]在LZTR1基因中，与RAS/MAPK通路相关，病人和他的兄弟。此外，患者因脑肿瘤而出现失语和右侧瘫痪。RNA测序揭示了与氧化应激相关的几个基因的显着上调，如活性氧途径和氧化磷酸化，RAS/MAPK通路的下游效应物，在病人和他的兄弟与健康志愿者相比。最终诊断为LZTR1相关家族性SWN,并且该患者的RAS/MAPK通路失调可能与脑肿瘤的发生有关。
