Leter Edward M, Koopmans A Karijn, Gille Johan J P, van Os Theo A M, Vittoz Gabriëlle G, David Eric F L, Jaspars Elisabeth H, Postmus Pieter E, van Moorselaar R Jeroen A, Craanen Mikael E, Starink Theo M, Menko Fred H
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
J Invest Dermatol. 2008 Jan;128(1):45-9. doi: 10.1038/sj.jid.5700959. Epub 2007 Jul 5.
Birt-Hogg-Dubé syndrome (BHD) is an autosomal-dominant genodermatosis characterized by skin fibrofolliculomas and an increased risk of spontaneous pneumothorax, renal and possibly other tumors. A causative gene (FLCN) on chromosome 17p has recently been identified. We here report clinical and genetic studies of 20 BHD families ascertained by the presence of multiple fibrofolliculomas or trichodiscomas in the proband. Pathogenic FLCN germline mutations were found in 11 (69%) of 16 probands tested and in 14 family members. Six different FLCN germline mutations were detected, four of which have not been reported previously. The clinical features were variable. None and less than 10 skin lesions were observed in two mutation carriers at the age of 67 and 29 years, respectively. Spontaneous pneumothorax was reported in four and renal carcinoma of mixed histological types in two of 36 BHD-affected individuals and/or FLCN mutation carriers. Both the prevalence of spontaneous pneumothorax and renal tumors appeared to be relatively low compared with previously reported data. Various other extracutaneous tumors were observed in 11 of 36 BHD-affected individuals and/or FLCN mutation carriers. This study of the second largest cohort to date contributes to the expanding data on the variable phenotype and underlying gene defects in BHD.
Birt-Hogg-Dubé综合征（BHD）是一种常染色体显性遗传性皮肤病，其特征为皮肤纤维毛囊瘤以及自发性气胸、肾脏肿瘤和可能的其他肿瘤发病风险增加。17号染色体短臂上的致病基因（FLCN）最近已被确定。我们在此报告了对20个BHD家族的临床和遗传学研究，这些家族是通过先证者存在多个纤维毛囊瘤或毛发盘状瘤而确定出来的。在16名接受检测的先证者中的11名（69%）以及14名家族成员中发现了致病性FLCN种系突变。检测到6种不同的FLCN种系突变，其中4种此前未曾报道过。临床特征具有变异性。分别在两名年龄为67岁和29岁的突变携带者中未观察到皮肤病变以及观察到少于10处皮肤病变。在36名受BHD影响的个体和/或FLCN突变携带者中，有4人报告发生了自发性气胸，2人报告发生了组织学类型混合的肾癌。与先前报告的数据相比，自发性气胸和肾脏肿瘤的患病率似乎相对较低。在36名受BHD影响的个体和/或FLCN突变携带者中的11人身上观察到了各种其他皮肤外肿瘤。这项对迄今为止第二大研究队列开展的研究有助于扩充有关BHD可变表型和潜在基因缺陷的数据。
