BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports.
BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports.
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BHD突变，Birt-Hogg-Dubé综合征的临床和分子遗传研究：一个新的50个家庭系列和已发表报告的评论。
DOI：
10.1136/jmg.2007.054304
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发表时间：
2008-06
影响因子：
4
通讯作者：
Linehan, W. M.
中科院分区：
文献类型：
--
作者：
Toro, J. R.;Wei, M-H;Glenn, G. M.;Weinreich, M.;Toure, O.;Vocke, C.;Turner, M.;Choyke, P.;Merino, M. J.;Pinto, P. A.;Steinberg, S. M.;Schmidt, L. S.;Linehan, W. M.
Birt-Hogg-Dubé综合征（BHDS）（MIM 135150）是一种常染色体显性遗传疾病，易发生滤泡性错构瘤（纤维滤泡瘤）、肺囊肿、自发性气胸和肾肿瘤。BHD的生殖系突变与BHDS的易感性相关。我们先前描述了51个BHD种系突变的BHDS家族。目的探讨1个既往报道的BHD家系和50个新的BHD家系的BHD突变谱、新的突变和新的临床特征。直接双向DNA测序用于筛选BHD基因中的突变，并通过亚克隆确认插入和缺失突变。我们通过比较人类与正向序列分析了卵泡素的进化保守性。BHD突变检出率为88%（51/58）。在鉴定的23种不同的种系突变中，13种是新的，包括：4个剪接位点，3个缺失，2个插入，2个无义，1个缺失/插入和1个错义突变。我们报告了一例双侧多灶性肾嗜酸细胞瘤患者的BHD c.1978A>G（K508 R）的第一个种系错义突变。这种突变发生在卵泡素中高度保守的氨基酸中。10%（5/51）的家庭成员没有组织学证实的纤维毛囊瘤。在根据皮肤病变确定的44个家庭中，有18个（41%）患有肾肿瘤。与没有阳性家族史的患者相比，具有生殖系BHD突变和肾癌家族史的患者发生肾肿瘤的概率在统计学上显著增加（p = 0.0032）。 同样，BHD种系突变和自发性气胸家族史的患者比无自发性气胸家族史的BHDS患者发生自发性气胸的概率显著增加（p = 0.011）。 对已发表的BHD生殖系突变病例报告进行了全面回顾。BHDS的特点是一系列的突变，和临床异质性之间和家庭内。
Birt–Hogg–Dubé syndrome (BHDS) (MIM 135150) is an autosomal dominant predisposition to the development of follicular hamartomas (fibrofolliculomas), lung cysts, spontaneous pneumothorax, and kidney neoplasms. Germline mutations in BHD are associated with the susceptibility for BHDS. We previously described 51 BHDS families with BHD germline mutations. To characterise the BHD mutation spectrum, novel mutations and new clinical features of one previously reported and 50 new families with BHDS. Direct bidirectional DNA sequencing was used to screen for mutations in the BHD gene, and insertion and deletion mutations were confirmed by subcloning. We analysed evolutionary conservation of folliculin by comparing human against the orthologous sequences. The BHD mutation detection rate was 88% (51/58). Of the 23 different germline mutations identified, 13 were novel consisting of: four splice site, three deletions, two insertions, two nonsense, one deletion/insertion, and one missense mutation. We report the first germline missense mutation in BHD c.1978A>G (K508R) in a patient who presented with bilateral multifocal renal oncocytomas. This mutation occurs in a highly conserved amino acid in folliculin. 10% (5/51) of the families had individuals without histologically confirmed fibrofolliculomas. Of 44 families ascertained on the basis of skin lesions, 18 (41%) had kidney tumours. Patients with a germline BHD mutation and family history of kidney cancer had a statistically significantly increased probability of developing renal tumours compared to patients without a positive family history (p = 0.0032). Similarly, patients with a BHD germline mutation and family history of spontaneous pneumothorax had a significantly increased greater probability of having spontaneous pneumothorax than BHDS patients without a family history of spontaneous pneumothorax (p = 0.011). A comprehensive review of published reports of cases with BHD germline mutation is discussed. BHDS is characterised by a spectrum of mutations, and clinical heterogeneity both among and within families.
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影响因子：
13.8
作者：
Liu, V;Kwan, T;Page, EH
通讯作者：
Page, EH
影响因子：
7.3
作者：
Murakami, T.;Sano, F.;Kishida, T.
通讯作者：
Kishida, T.
DOI：
10.1164/rccm.200501-143oc
发表时间：
2005-07-01
影响因子：
24.7
作者：
Graham, RB;Nolasco, M;Garcia, CK
通讯作者：
Garcia, CK
影响因子：
4
作者：
Gunji, Yoko;Akiyoshi, Taeko;Seyama, Kuniaki
通讯作者：
Seyama, Kuniaki
DOI：
10.1111/j.1349-7006.2001.tb02133.x
发表时间：
2001-11-01
期刊：
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子：
--
作者：
Hino, O;Okimoto, K;Sakurai, J
通讯作者：
Sakurai, J