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- PMID: 23072324
- UKPMCID: 23072324
- DOI: 10.1111/cen.12074
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Evaluation of SDHB, SDHD and VHL gene susceptibility testing in the assessment of individuals with non-syndromic phaeochromocytoma, paraganglioma and head and neck paraganglioma.
Jafri, Mariam; Whitworth, James; Rattenberry, Eleanor; Vialard, Lindsey; Kilby, Gail; Kumar, Ajith V; Izatt, Louise; Lalloo, Fiona; Brennan, Paul; Cook, Jackie; Morrison, Patrick J; Canham, Natalie; Armstrong, Ruth; Brewer, Carole; Tomkins, Susan; Donaldson, Alan; Barwell, Julian; Cole, Trevor R; Atkinson, A Brew; Aylwin, Simon; Ball, Steve G; Srirangalingam, Umasuthan; Chew, Shern L; Evans, Dafydd Gareth R; Hodgson, Shirley V; Irving, Richard; Woodward, Emma; Macdonald, Fiona; Maher, Eamonn R
Clinical endocrinology. 2013;78(6):898-906.
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Full-text held externally
- PMID: 23072324
- UKPMCID: 23072324
- DOI: 10.1111/cen.12074
Abstract
OBJECTIVES: Research studies have reported that about a third of individuals with phaeochromocytoma/paraganglioma (PPGL) have an inherited predisposition, although the frequency of specific mutations can vary between populations. We evaluated VHL, SDHB and SDHD mutation testing in cohorts of patients with non-syndromic PPGL and head and neck paraganglioma (HNPGL). DESIGN: Prospective, observational evaluation of NHS practice. PATIENTS: Individuals with PPGL/HNPGL referred to a supraregional genetics testing service over a 10-year period. MEASUREMENTS: Clinical (age, tumour site, malignancy, etc.), mutation frequencies and characteristics. RESULTS: A total of 501 probands with PPGL (n = 413) or HNPGL (n = 88) were studied. Thirty-one percent of patients with PPGL presented had a pathogenic mutation in SDHB, SDHD or VHL. Mutation detection rates were highest in those with a positive family history (62%), malignancy (53%), multiple tumours (33%) or PGL (44%). Twenty-eight percent of individuals with a single sporadic phaeochromocytoma had a mutation. Overall, 63% of patients with HNPGL had a mutation (92% of those with a family history, 89% of those with multicentric tumours and 34% of those with a single sporadic HNPGL). Penetrance was calculated in 121 SDHB mutation-positive probands and 187 of their mutation-positive relatives. Most relatives were asymptomatic and lifetime penetrance in non-proband SDHB mutation carriers was <50%. CONCLUSIONS: Practice-based evaluations of genetic testing in PPGL reveal high mutation detection rates. Although clinical criteria can be used to prioritize mutation testing, mutations were detected in 'low risk groups' indicating a need for comprehensive and inexpensive genetic testing strategies for PPGL and HNPGL.
Bibliographic metadata
- Jafri, Mariam
- Whitworth, James
- Rattenberry, Eleanor
- Vialard, Lindsey
- Kilby, Gail
- Kumar, Ajith V
- Izatt, Louise
- Lalloo, Fiona
- Brennan, Paul
- Cook, Jackie
- Morrison, Patrick J
- Canham, Natalie
- Armstrong, Ruth
- Brewer, Carole
- Tomkins, Susan
- Donaldson, Alan
- Barwell, Julian
- Cole, Trevor R
- Atkinson, A Brew
- Aylwin, Simon
- Ball, Steve G
- Srirangalingam, Umasuthan
- Chew, Shern L
- Evans, Dafydd Gareth R
- Hodgson, Shirley V
- Irving, Richard
- Woodward, Emma
- Macdonald, Fiona
- Maher, Eamonn R