Case Report of Birt-Hogg-Dubé Syndrome: Germline Mutations of FLCN Detected in Patients With Renal Cancer and Thyroid Cancer.
Case Report of Birt-Hogg-Dubé Syndrome: Germline Mutations of FLCN Detected in Patients With Renal Cancer and Thyroid Cancer.
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DOI：
10.1097/md.0000000000003695
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发表时间：
2016-05
期刊：
影响因子：
1.6
通讯作者：
Yu Y
中科院分区：
文献类型：
--
作者：
Dong L;Gao M;Hao WJ;Zheng XQ;Li YG;Li XL;Yu Y
Birt-Hogg-Dubé（BHD）是一种罕见的常染色体显性遗传综合征，其特征是存在纤维毛囊瘤和/或椎间盘、肺囊肿、自发性气胸和肾肿瘤。在这里，我们报告的2例肾细胞癌和皮肤病学特征的患者被怀疑患有BHD综合征。将这些患者的血液样品送去通过桑格测序进行全外显子测序。2例患者FLCN基因共检测到8个突变，其中5个位于非编码区，1个同义突变，2个错义突变。2个错义突变经MutationTaster和SIFT预测为致病突变或影响蛋白质功能，证实了诊断。此外，2例患者还患有甲状腺乳头状癌。行甲状腺全切除术和预防性双侧中央淋巴结清扫术，BHD-2还接受了外侧淋巴结清扫术。病理报告显示，尽管甲状腺病灶很小，但患者有淋巴结转移。这2个突变均为以前未见报道的突变，扩大了BHD综合征相关FLCN基因的突变谱。对合并BHD综合征的甲状腺癌患者，甲状腺全切除术和预防性双侧中央淋巴结清扫术是可行的，颈部超声检查对BHD患者及其家属有一定的益处。
Birt–Hogg–Dubé (BHD) is a rare autosomal dominant inherited syndrome that is characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. Here, the 2 patients we reported with renal cell carcinomas and dermatological features were suspected to be suffering from BHD syndrome. Blood samples of these patients were sent for whole exon sequencing performed by Sanger sequencing. Eight mutations, including 5 mutations, which were mapped in noncoding region, 1 synonymous mutation, and 2 missense mutations, were detected in the FLCN gene in both patients. The 2 missense mutations, predicted to be disease-causing mutation or affecting protein function by MutationTaster and SIFT, confirmed the diagnosis. In addition, the 2 patients were also affected with papillary thyroid cancer. Total thyroidectomy and prophylactic bilateral central lymph node dissection were performed for them and the BHD-2 also received lateral lymph node dissection. Pathology reports showed that the patients had lymph node metastasis in spite of small size of thyroid lesions. The 2 missense mutations, not reported previously, expand the mutation spectrum of FLCN gene associated with BHD syndrome. For the thyroid cancer patients with BHD syndrome, total thyroidectomy and prophylactic bilateral central lymph node dissection may be suitable and the neck ultrasound may benefit BHD patients and their family members.