SMARCB1/INI1 种系突变导致 10%的散发神经鞘瘤病。
SMARCB1/INI1 germline mutations contribute to 10% of sporadic schwannomatosis.
机构信息
Laboratory of Molecular Oncogenetics, Institut Paoli-Calmettes, Marseille, France.
出版信息
BMC Neurol. 2011 Jan 24;11:9. doi: 10.1186/1471-2377-11-9.
BACKGROUND
Schwannomatosis is a disease characterized by multiple non-vestibular schwannomas. Although biallelic NF2 mutations are found in schwannomas, no germ line event is detected in schwannomatosis patients. In contrast, germline mutations of the SMARCB1 (INI1) tumor suppressor gene were described in familial and sporadic schwannomatosis patients.
METHODS
To delineate the SMARCB1 gene contribution, the nine coding exons were sequenced in a series of 56 patients affected with a variable number of non-vestibular schwannomas.
RESULTS
Nine variants scattered along the sequence of SMARCB1 were identified. Five of them were classified as deleterious. All five patients carrying a SMARCB1 mutation had more multiple schwannomas, corresponding to 10.2% of patients with schwannomatosis. They were also diagnosed before 35 years of age.
CONCLUSIONS
These results suggest that patients with schwannomas have a significant probability of carrying a SMARCB1 mutation. Combined with data available from other studies, they confirm the clinical indications for genetic screening of the SMARCB1 gene.
背景
神经鞘瘤病是一种以多发性非前庭神经鞘瘤为特征的疾病。虽然神经鞘瘤中存在双等位 NF2 突变，但在神经鞘瘤病患者中并未检测到种系事件。相比之下，SMARCB1（INI1）肿瘤抑制基因的种系突变已在家族性和散发性神经鞘瘤病患者中描述。
方法
为了描绘 SMARCB1 基因的贡献，对 56 名患有不同数量非前庭神经鞘瘤的患者的九个编码外显子进行了测序。
结果
确定了散布在 SMARCB1 序列中的九个变体。其中五个被归类为有害。所有携带 SMARCB1 突变的五名患者均有多发性神经鞘瘤，占神经鞘瘤病患者的 10.2%。他们也在 35 岁之前被诊断出来。
结论
这些结果表明，患有神经鞘瘤的患者有很大的可能性携带 SMARCB1 突变。结合其他研究提供的数据，它们证实了对 SMARCB1 基因进行遗传筛查的临床指征。
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