Molecular characterisation of a common SDHB deletion in paraganglioma patients

Abstract

After haplotyping the SDHB region, we concluded that the deletion detected in Iberian Peninsular people is probably due to a founder effect. Regarding the clinical characteristics of patients with this alteration, it seems that the presence of gross deletions rather than point mutations is more likely related to abdominal presentations and younger age at onset. Moreover, we found for the first time a patient with neuroblastoma and a germline SDHB deletion, but it seems that this paediatric neoplasia in a pheochromocytoma family is not a key component of this disease.

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

“…two occurred in exon 1 of SDHB, including one of approximately 20 kb, previously demonstrated by Cascon et al [12]. Consequently, the frequency of SDHB deletion across all French SDHB positive cases was estimated at 8.3% (8/96).…”

“…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.…”

“…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].…”

Mitochondrial metabolic remodeling in response to genetic and environmental perturbations

“…Since the initial discovery of SDHD mutations in 2000, mutations in SDHB and SDHC , and more recently, SDHA and SDHAF2 (encoding the protein responsible for FAD incorporation into SDH) have been identified with the same syndrome 47, 48, 49, 60. These mutations are found as heterozygous germline mutations, which means that loss of protein function and neoplastic transformation develops as a result of loss of heterozygosity, resulting in the complete loss of enzyme function by a second ‘hit.’61 Inactivating mutations of SDH subunits have since been reportedly associated with other tumor types including gastrointestinal stromal tumors,62 renal cell carcinoma,63, 64 and neuroblastoma 65, 66. Interestingly, mutations of SDHB predispose to a more malignant and aggressive form of paraganglioma than those of the other subunits, despite the apparent similarities in both functional and downstream phenotypic consequences of this mutation.…”

Identification of a 4.9-kilo base-pair Alu-mediated founder SDHD deletion in two extended paraganglioma families from Austria

“…19 Large germline founder deletions in SDHB and SDHC were characterized at the sequence level in multiple unrelated subjects from Spain and the United States, respectively. 9,12,20 Complete gene deletions in SDHD were described in two studies using multiplex PCR amplification and quantification of gene exons. 21,22 These studies, however, did not characterize the precise extent of SDHD deletions by identifying the DNA sequences spanning the deletion break points.…”