A novel G106D alteration of the SDHD gene in a pedigree with familial paraganglioma

Kazumi Ogawa, Kiyoto Shiga, Shigeru Saijo, Takenori Ogawa, Noriko Kimura, Akira Horii

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Head and neck paragangliomas are tumors derived from parasympathetic paraganglia. Familial cases account for 10% or more of these tumors, and mutations of the genes encoding subunits for the mitochondrial respiratory chain complex II, SDHD, SDHB, and SDHC, have been reported. We analyzed mutations in the all four SDH genes, SDHA through SDHD, in a Japanese family with cervical paraganglioma that include a father with bilateral tumors and his daughter with a malignant left carotid body tumor with nodal metastasis. This pedigree harbored a germline G106D alteration in exon 4 of the SDHD gene that has not previously been reported to date. The tumors of the father expressed biallelic SDHD. but the SDHD expression was highly suppressed by an unknown mechanism(s) in tumors of his daughter, and the wild-type allele was predominantly suppressed in the metastatic node. These results suggest that the missense dysfunction of SDHD prepares neoplastic condition and that expressional silencing, particularly of the wild-type allele, plays an important role in the malignant transformation of the paragangliomas. Our results may lead to a better understanding of this disease and to the development of methods for prevention of this disease.

Original languageEnglish
Pages (from-to)2441-2446
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Issue number22
Publication statusPublished - 2006 Nov 15


  • Familial paraganglioma
  • Mitochondrial complex II
  • SDHD

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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