Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene
Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene
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DOI：
10.1002/gcc.1144
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发表时间：
2001-07-01
影响因子：
3.7
通讯作者：
Devilee, P
中科院分区：
文献类型：
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作者：
Taschner, PEM;Jansen, JC;Devilee, P
遗传性副神经节瘤或血管球瘤通常是头颈部的良性肿瘤，生长缓慢。遗传性副神经节瘤的遗传方式为常染色体显性遗传并伴有印记。最近，我们已经确定了SDHD基因编码的线粒体呼吸链复合体II的亚基D参与遗传性副神经节瘤的基因之一。在这里，我们证明了两个创始人突变，Asp 92 Tyr和Leu 139 Pro，负责副神经节瘤在24和6的32个独立确定的荷兰副神经节瘤家族，分别。在55例孤立患者中的20例中也检测到这两种突变。其中10名孤立的患者患有多发性副神经节瘤，在其中8名SDHD患者中发现了种系突变，表明多中心性是孤立患者中该疾病遗传性质的强预测因素。此外，我们还证明了在携带突变的患者的肿瘤中，母源性野生型SDHD等位基因丢失，这表明SDHD具有肿瘤抑制基因的功能。(C)2001 Wiley-Liss，Inc.
Hereditary paragangliomas or glomus tumors are usually benign slow-growing rumors in the head and neck region. The inheritance pattern of hereditary paraganglioma is autosomal dominant with imprinting. Recently, we have identified the SDHD gene encoding subunit D of the mitochondrial respiratory chain complex II as one of the genes involved in hereditary paragangliomas. Here, we demonstrate that two founder mutations, Asp92Tyr and Leu139Pro, are responsible for paragangliomas in 24 and 6 of the 32 independently ascertained Dutch paraganglioma families, respectively. These two mutations were also detected among 20 of 55 isolated patients. Ten of the isolated patients had multiple paragangliomas, and in eight of these SDHD germline mutations were found, indicating that multicentricity is a strong predictive factor for the hereditary nature of the disorder in isolated patients. in addition, we demonstrate that the maternally derived wild-type SDHD allele is lost in tumors from mutation-carrying patients, indicating that SDHD functions as a tumor suppressor gene. (C) 2001 Wiley-Liss, Inc.