The first Dutch SDHB founder deletion in paraganglioma – pheochromocytoma patients

Abstract

Background: Germline mutations of the tumor suppressor genes SDHB, SDHC and SDHD play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydrogenase (SDH), the mitochondrial tricarboxylic acid cycle enzyme and complex II component of the electron transport chain. The majority of variants of the SDH genes are missense and nonsense mutations. To date few large deletions of the SDH genes have been described.

Molecular characterization of novel germline deletions affecting SDHD and SDHC in pheochromocytoma and paraganglioma patients

“…Deletion analysis of SDHD and SDHC by MLPA detected four deletions in a point mutation-negative group of 126 patients, so deletions of these genes represent 3% of all mutations identified. We have described a founder deletion of exon 3 of the SDHB gene in nine patients of this same group of point mutation-negative patients (Bayley et al 2009). While founder mutations are common in the Dutch population , Zeegers et al 2004, as once again shown by the identification of the SDHB exon 3 deletion, other populations also show founder effects (Cascon et al 2008, Peczkowska et al 2008b, Opocher et al 2009), indicating that while the general frequency of SDH deletions across all paraganglioma patient populations cannot yet be established, the proportion of deletions found in the Dutch population may have wider relevance.…”

“…Another patient (patient 4) showed J-P Bayley et al: Deletions of SDHD and SDHC www.endocrinology-journals.org deletion of SDHC exons 5 and 6. A founder deletion of exon 3 of the SDHB gene was identified in nine patients and has been described elsewhere (Bayley et al 2009). When all 13 patients with SDHB, SDHC, or SDHD deletions are taken in to account, deletions (13/138) represented w10% of all mutations identified in index patients, indicating that deletions can represent a significant proportion of all mutations in paraganglioma (PGL) patient groups (Table 1).…”

A Large Deletion in the Succinate Dehydrogenase B Gene (SDHB) in a Japanese Patient with Abdominal Paraganglioma and Concomitant Metastasis

“…while the majority of patients undergoing SDHB mutation analysis have missense and nonsense mutations, some mutation negative patients have been reported to carry either large partial or total deletions of the SDHB gene [10][11][12][13][14][15][16][17][18]. to investigate this possibility, we carried out MLPA and identified a heterozygous SDHB gene deletion encompassing sequences corresponding to the promoter region, exon 1 and exon 2 ( Fig.…”

“…Given that only a small number of SDHB deletion cases have been described [10][11][12][13][14][15][16][17][18], it is difficult to meaningfully compare the phenotypes and penegest to us that these tests capable of detecting such large deletions, such as MLPA, should be made routine. Conceivably, MLPA could be used to screen for large deletions in all three SDHx genes in a single test.…”

“…Since large deletions are rare and are undetectable using this method, neither the frequency nor the clinical manifestation associated with large SDHB deletions is well known. recently, in addition to these mutations, the use of methods such as multiplex ligation-dependent probe amplification (MLPA) and quantitative multiplex PCR of short fluorescent fragments (QmPSF) have resulted in increased reports of large SDHB deletions [10][11][12][13][14][15][16][17][18].…”