Strizheva G D, Carsillo T, Kruger W D, Sullivan E J, Ryu J H, Henske E P
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Am J Respir Crit Care Med. 2001 Jan;163(1):253-8. doi: 10.1164/ajrccm.163.1.2005004.
Lymphangiomyomatosis (LAM) is a progressive and often fatal interstitial lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. LAM is of unusual interest biologically because it affects almost exclusively young women. LAM can occur as an isolated disorder (sporadic LAM) or in association with tuberous sclerosis complex (TSC). Because only a minority of women with TSC develops symptomatic LAM, we hypothesized that a relationship might exist between the type of germline TSC1 or TSC2 gene mutation and the risk of developing LAM. We examined all 41 exons of the TSC2 gene and 21 coding exons of the TSC1 gene for mutations in a group of 14 women with both TSC and LAM using single-strand conformation polymorphism analysis. Seven mutations were found in TSC2 and one in TSC1. Of the seven patients with TSC2 mutations, two had the same in-frame exon 40 deletion and one had an exon 41 missense change. We conclude that germline mutations in the extreme carboxy-terminus of tuberin can result in LAM. Further studies will be required to determine whether mutations in exons 40 and 41 are associated with an increased incidence and/or severity of LAM in women with TSC.
淋巴管平滑肌瘤病（LAM）是一种进行性且通常致命的间质性肺病，其特征是肺部异常平滑肌细胞的弥漫性增殖。LAM在生物学上具有特殊意义，因为它几乎只影响年轻女性。LAM可作为一种孤立性疾病（散发性LAM）出现，或与结节性硬化症（TSC）相关。由于只有少数患有TSC的女性会出现有症状的LAM，我们推测种系TSC1或TSC2基因突变类型与发生LAM的风险之间可能存在关联。我们使用单链构象多态性分析，对一组14名同时患有TSC和LAM的女性的TSC2基因的所有41个外显子和TSC1基因的21个编码外显子进行了突变检测。在TSC2中发现了7个突变，在TSC1中发现了1个突变。在7名有TSC2突变的患者中，2名有相同的框内第40外显子缺失，1名有第41外显子错义改变。我们得出结论，结节蛋白极端羧基末端的种系突变可导致LAM。需要进一步研究以确定第40和41外显子中的突变是否与患有TSC的女性中LAM的发病率增加和/或严重程度相关。
