Abstract：
Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN). It is characterized by skin tumors, multiple lung cysts, and renal tumors. Active genetic testing and appropriate periodic examinations of family lines of patients with BHD syndrome have not been widely performed. In this report, we present our experience regarding the diagnosis of asymptomatic family members with BHD syndrome. The proband was a 65-year-old female with a family history of colorectal cancer and spontaneous pneumothorax that affected her father. Computed tomography revealed an approximately 10 cm-sized tumor protruding from the upper pole of the left kidney, a buried tumor approximately 1.5 cm in length in the right kidney, and multiple pulmonary cysts. The patient underwent laparoscopic radical left nephrectomy. Pathological examination indicated that the resected tumor was a chromophobe renal cell carcinoma. After the surgery, there was no evidence of local recurrence or metastasis. The size of the tumor in the right kidney was monitored, but it did not increase. On FLCN genetic examination, targeted next generation sequencing revealed a partial deletion of exon 14, thus confirming the diagnosis of the patient to be BHD syndrome that caused the previously unreported pathogenic variant. Three years after the surgery, we conducted genetic counseling for the proposita and her three children. Genetic examination, performed at the request of the second daughter, confirmed that she carried the same genetic variant as her mother. This diagnosis prompted the second daughter to begin managing her health via periodic imaging tests.
摘要：
Birt-Hogg-Dubé（BHD）综合征是由卵泡蛋白基因（FLCN）的种系突变引起的常染色体显性疾病。它的特点是皮肤肿瘤，多发性肺囊肿,还有肾肿瘤.尚未广泛进行BHD综合征患者的积极遗传检测和适当的定期检查。在这份报告中,我们介绍了我们对无症状的BHD综合征家庭成员的诊断经验.先证者是一名65岁的女性，有影响其父亲的结直肠癌和自发性气胸的家族史。计算机断层扫描显示一个大约10厘米大小的肿瘤从左肾上极突出，一个埋藏在右肾长度约1.5厘米的肿瘤，和多发性肺囊肿.患者接受腹腔镜根治性左肾切除术。病理检查显示切除的肿瘤为肾嫌色细胞癌。手术后,没有局部复发或转移的证据.监测了右肾肿瘤的大小,但并没有增加。关于FLCN基因检查，靶向的下一代测序显示外显子14部分缺失,从而证实患者被诊断为BHD综合征,该综合征导致了以前未报告的致病变异.手术三年后,我们对proposita和她的三个孩子进行了遗传咨询。基因检查,在第二个女儿的要求下表演，证实她携带与母亲相同的遗传变异。这种诊断促使第二个女儿开始通过定期成像测试来管理她的健康。
