Analysis of the SDHD gene, the susceptibility gene for familial paraganglioma syndrome (PGL1), in pheochromocytomas.

Abstract

Pheochromocytomas are neural crest-derived tumors that occur mostly sporadically, but may also be part of inherited syndromes. The molecular pathogenesis of sporadic pheochromocytomas remains unknown. Recently, the susceptibility gene for familial paraganglioma syndrome, a disorder embryologically related to pheochromocytomas, was characterized and shown to encode the small subunit of succinate dehydrogenase (SDHD), which is part of the mitochondrial complex II. This complex regulates oxygen-sensing signals. Importantly, hypoxic signals also appear to be related to the pathogenesis of pheochromocytomas associated with von Hippel-Lindau syndrome. We sequenced the entire coding region of the SDHD gene in a series of pheochromocytomas. Although we did not find mutations in the gene, we identified a new intronic single nucleotide polymorphism in 15% of the samples (g.97739A-->G). We also confirmed the existence of a sequence highly homologous to the SDHD complementary DNA in chromosome 1p34--36, a region commonly deleted in pheochromocytomas. Full analysis of this sequence revealed a heterozygous single base substitution in 70% of our samples that was also present in the germline. This sequence does not appear to be transcribed and is probably a processed pseudogene. Therefore, despite its chromosomal location, it is unlikely that this sequence is a target of loss of heterozygosity in pheochromocytomas. In conclusion, mutations of the SDHD gene are not a common event in this series of sporadic pheochromocytomas. The existence of SDHD pseudogenes should be considered when analyzing complementary DNA-based samples.

• Authors: R C Aguiar, G Cox, S L Pomeroy, P L Dahia
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 86 Issue 6 Pg. 2890-4 (Jun 2001) ISSN: 0021-972X [Print] United States
• PMID: 11397905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Membrane Proteins
• SDHD protein, human
• Succinate Dehydrogenase

Topics

• Adrenal Gland Neoplasms (genetics)
• Amino Acid Sequence (genetics)
• Base Sequence (genetics)
• Chromosomes, Human, Pair 1 (genetics)
• Genetic Predisposition to Disease (genetics)
• Humans
• Membrane Proteins (genetics)
• Molecular Sequence Data
• Paraganglioma (genetics)
• Pheochromocytoma (genetics)
• Polymorphism, Genetic (genetics)
• Pseudogenes (genetics)
• Succinate Dehydrogenase
• Syndrome
• Transcription, Genetic