Smolarek T A, Wessner L L, McCormack F X, Mylet J C, Menon A G, Henske E P
Department of Molecular Genetics, Biochemistry and Microbiologyk University of Cincinnati, Cincinnati, OH, USA.
Am J Hum Genet. 1998 Apr;62(4):810-5. doi: 10.1086/301804.
Lymphangiomyomatosis (LAM) is a rare disease, of unknown etiology, affecting women almost exclusively. Lung transplantation is the only consistently effective therapy for LAM. Microscopically, LAM consists of a diffuse proliferation of smooth muscle cells. LAM can occur without evidence of other disease (referred to as "sporadic LAM") or in association with tuberous sclerosis complex (TSC). TSC is an autosomal dominant tumor suppressor gene syndrome characterized by seizures, mental retardation, and tumors in the brain, heart, skin, and kidney. Renal angiomyolipomas occur in approximately 50% of sporadic LAM patients and in 70% of TSC patients. Loss of heterozygosity (LOH) in the chromosomal region for the TSC2 gene occurs in 60% of TSC-associated angiomyolipomas. Because of the similar pulmonary and renal manifestations of TSC and sporadic LAM, we hypothesized that LAM and TSC have a common genetic basis. We analyzed renal angiomyolipomas, from 13 women with sporadic LAM, for LOH in the regions of the TSC1 (chromosome 9q34) and TSC2 (chromosome 16p13) genes. TSC2 LOH was detected in seven (54%) of the angiomyolipomas. We also found TSC2 LOH in four lymph nodes from a woman with retroperitoneal LAM. No TSC1 LOH was found. Our findings indicate that the TSC2 gene may be involved in the pathogenesis of sporadic LAM. However, genetic transmission of LAM has not been reported. Women with LAM may have low-penetrance germ-line TSC2 mutations, or they may be mosaic, with TSC2 mutations in the lung and the kidney but not in other organs.
淋巴管平滑肌瘤病（LAM）是一种病因不明的罕见疾病，几乎仅累及女性。肺移植是LAM唯一持续有效的治疗方法。在显微镜下，LAM由平滑肌细胞的弥漫性增殖构成。LAM可在无其他疾病证据的情况下发生（称为“散发性LAM”），或与结节性硬化症（TSC）相关。TSC是一种常染色体显性肿瘤抑制基因综合征，其特征为癫痫发作、智力发育迟缓以及脑、心脏、皮肤和肾脏出现肿瘤。肾血管平滑肌脂肪瘤在大约50%的散发性LAM患者和70%的TSC患者中出现。TSC2基因所在染色体区域的杂合性缺失（LOH）在60%的与TSC相关的肾血管平滑肌脂肪瘤中出现。由于TSC和散发性LAM在肺部和肾脏表现相似，我们推测LAM和TSC有共同的遗传基础。我们分析了13例散发性LAM女性患者的肾血管平滑肌脂肪瘤，检测TSC1（9号染色体q34）和TSC2（16号染色体p13）基因区域的LOH。在7个（54%）肾血管平滑肌脂肪瘤中检测到TSC2 LOH。我们还在一名患有腹膜后LAM的女性的4个淋巴结中发现了TSC2 LOH。未发现TSC1 LOH。我们的研究结果表明，TSC2基因可能参与散发性LAM的发病机制。然而，LAM的遗传传递尚未见报道。患有LAM的女性可能有低外显率的生殖系TSC2突变，或者她们可能是嵌合体，肺部和肾脏有TSC2突变，但其他器官没有。
