Clinical and genetic spectrum of Birt-Hogg-Dube syndrome patients in whom pneumothorax and/or multiple lung cysts are the presenting feature.
Clinical and genetic spectrum of Birt-Hogg-Dube syndrome patients in whom pneumothorax and/or multiple lung cysts are the presenting feature.
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DOI：
10.1136/jmg.2009.070565
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发表时间：
2010-04
影响因子：
4
通讯作者：
Seyama K
中科院分区：
文献类型：
--
作者：
Kunogi M;Kurihara M;Ikegami TS;Kobayashi T;Shindo N;Kumasaka T;Gunji Y;Kikkawa M;Iwakami S;Hino O;Takahashi K;Seyama K
Birt-Hogg-Dubé 综合征 (BHDS) 是一种遗传性常染色体遗传性皮肤病，以皮肤纤维毛囊瘤、肾肿瘤和多发性肺囊肿为特征。遗传学研究表明，临床表现以及相关的种系 FLCN 突变是多种多样的。 BHDS 可能是由常规遗传方法无法检测到的种系缺失引起的。实时定量聚合酶链反应（qPCR）也许能够识别这种突变，从而为我们提供更准确的 BHDS 临床图像。 这项研究分析了 36 名不明原因的多发性肺囊肿患者。应用变性高效液相色谱（DHPLC）进行突变筛选。如果DHPLC未检测到异常，则通过qPCR对基因组中每个FLCN外显子的量进行定量。 通过 DHPLC 和直接测序（13 个独特的小核苷酸改变，其中包括 11 个新突变），在 36 名患者中的 23 名（63.9%）中发现了 FLCN 种系突变。通过 qPCR，在其余 13 名患者中的两名中发现了大的基因组缺失（一名患者存在外显子 14 缺失，另一名患者存在包含外显子 9 至 14 的缺失）。包括基因组缺失在内的突变最常见于 FLCN 基因的 3' 端，包括外显子 12 和 13 (13/25=52.0%)。在本研究中，多发性囊肿提示诊断的 BHDS 患者皮肤和肾脏受累的发生率非常低。 BHDS 是由于大的缺失和小的核苷酸改变造成的。日本人和欧洲人后裔的患者在 FLCN 突变和临床表现方面可能存在种族差异。
Birt–Hogg–Dubé syndrome (BHDS) is an inherited autosomal genodermatosis characterised by fibrofolliculomas of the skin, renal tumours and multiple lung cysts. Genetic studies have disclosed that the clinical picture as well as responsible germline FLCN mutations are diverse. BHDS may be caused by a germline deletion which cannot be detected by a conventional genetic approach. Real-time quantitative polymerase chain reaction (qPCR) may be able to identify such a mutation and thus provide us with a more accurate clinical picture of BHDS. This study analysed 36 patients with multiple lung cysts of undetermined causes. Denaturing high performance liquid chromatography (DHPLC) was applied for mutation screening. If no abnormality was detected by DHPLC, the amount of each FLCN exon in genome was quantified by qPCR. An FLCN germline mutation was found in 23 (63.9%) of the 36 patients by DHPLC and direct sequencing (13 unique small nucleotide alterations which included 11 novel mutations). A large genomic deletion was identified in two of the remaining 13 patients by qPCR (one patient with exon 14 deletion and one patient with a deletion encompassing exons 9 to 14). Mutations including genomic deletions were most frequently identified in the 3′-end of the FLCN gene including exons 12 and 13 (13/25=52.0%). The BHDS patients whose multiple cysts prompted the diagnosis in this study showed a very low incidence of skin and renal involvement. BHDS is due to large deletions as well as small nucleotide alterations. Racial differences may occur between Japanese and patients of European decent in terms of FLCN mutations and clinical manifestations.
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影响因子：
2.4
作者：
Plawski, Andrzej;Slomski, Ryszard
通讯作者：
Slomski, Ryszard
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
影响因子：
3.9
作者：
Gavert, Nancy;Yaron, Yuval;Orr-Urtreger, Avi
通讯作者：
Orr-Urtreger, Avi
影响因子：
--
作者：
Damgaard, D;Nissen, PH;Faergeman, O
通讯作者：
Faergeman, O