SFEBES2008 Poster Presentations Endocrine tumours and neoplasia (31 abstracts)
A succinate dehydrogenase B (SDHB) founder mutation
Katherine Hughes 1 , Lindsay McDougall 2 , Nicola Bradshaw 2 , Colin Perry 1 , Robert Lindsay 1 , Michelle McConachie 3 , D Fraser Davidson 4 , Victoria Murday 2 & John M C Connell 1
1Division of Cardiovascular and Medical Sciences, Western Infirmary, Glasgow, Lanarkshire, UK; 2West of Scotland Regional Genetics Service, Glasgow, Lanarkshire, UK; 3Molecular Genetics Laboratory, Dundee, Tayside, UK; 4Biochemistry Department, Crosshouse Hospital, Kilmarnock, Ayrshire, UK.
Phaeochromocytomas (PHAEO)/paragangliomas (PGL) are neuro-endocrine tumours. They may present sporadically or as the primary abnormality in a number of familial syndromes. Advances in molecular genetics have led to the identification of several PHAEO/PGL predisposing genes including VHL, NF1 and RET. Mutations in the genes encoding the subunits of Succinate Dehydrogenase (SDH) have also been reported. We describe the phenotype of a cohort of patients with a Succinate Dehydrogenase B (SDHB) mutation that is predicted to disrupt the normal splicing of exon 1.
Seven families with the IVS1+1G>T mutation were identified; six after presentation of the index cases to our centre, and one after an individual in Australia was found to have the mutation and reported relatives in our region. Fifteen unaffected relatives of index cases were tested. Nine of these individuals were found to have the mutation but had no clinical or biochemical features of catecholamine excess. Of the affected index cases, the tumours were mainly secretory, intra-abdominal extra-adrenal tumours. Two-thirds were malignant. Haplotype analysis identified a common haplotype in six of the seven families confirming that the mutation is likely to have been inherited from a common ancestor. The seventh individual shared part of the haplotype.
Although the inheritance pattern is autosomal dominant, we found that there was incomplete penetrance and variable expressivity in the phenotype of individuals with the mutation. Whilst studies to demonstrate the molecular effects of this mutation are awaited, the presence of typical PHAEO/PGL, and the absence of any other mutation on molecular testing support the notion that this is the causal mutation in these individuals with PHAEO/PGL.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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