Germline SDHD mutation in paraganglioma of the spinal cord

Abstract

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.