Masuoka J, Brandner S, Paulus W, Soffer D, Vital A, Chimelli L, Jouvet A, Yonekawa Y, Kleihues P, Ohgaki H
International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon, Cedex 08, France.
Oncogene. 2001 Aug 16;20(36):5084-6. doi: 10.1038/sj.onc.1204579.
Hereditary paraganglioma of the head and neck is associated with germline mutations in the SDHD gene, which encodes a mitochondrial respiratory chain protein. Paragangliomas of the central nervous system are very rare, occur almost exclusively in the cauda equina of the spinal cord and are considered non-familial. In the present study, we screened 22 apparently sporadic paragangliomas of the cauda equina for SDHD mutations. One spinal paraganglioma and similar cerebellar tumours that developed 22 years later in the same patient contained a missense mutation at codon 12 (GGT-->AGT, Gly-->Ser) and a silent mutation at codon 68 (AGC-->AGT, Ser-->Ser). There was no family history of paragangliomas but DNA from white blood cells of this patient showed the same sequence alterations, indicating the presence of a germline mutation. All other cases of spinal paraganglioma had the wild-type SDHD sequence, except one case with a silent mutation at codon 68 (AGC-->AGT, Ser-->Ser). This is the first observation indicating that inherited SDHD mutations may occasionally cause the development of paragangliomas in the central nervous system.
头颈部遗传性副神经节瘤与SDHD基因的种系突变有关，该基因编码一种线粒体呼吸链蛋白。中枢神经系统的副神经节瘤非常罕见，几乎仅发生于脊髓马尾，且被认为是非家族性的。在本研究中，我们筛查了22例明显散发的马尾副神经节瘤的SDHD突变情况。同一患者22年后发生的1例脊髓副神经节瘤及类似的小脑肿瘤，在密码子12处存在错义突变（GGT→AGT，甘氨酸→丝氨酸），在密码子68处存在沉默突变（AGC→AGT，丝氨酸→丝氨酸）。该患者无副神经节瘤家族史，但来自其白细胞的DNA显示出相同的序列改变，表明存在种系突变。除1例在密码子68处存在沉默突变（AGC→AGT，丝氨酸→丝氨酸）外，所有其他脊髓副神经节瘤病例的SDHD序列均为野生型。这是首次观察到遗传性SDHD突变可能偶尔导致中枢神经系统副神经节瘤的发生。
