Outcomes of annual surveillance imaging in an adult and paediatric cohort of succinate dehydrogenase B mutation carriers

2016 ◽  
Vol 86 (2) ◽  
pp. 286-296 ◽  
Author(s):  
Nicola Tufton ◽  
Lucy Shapiro ◽  
Umasuthan Srirangalingam ◽  
Polly Richards ◽  
Anju Sahdev ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Mutation Carriers ◽  
Surveillance Imaging ◽  
Paediatric Cohort

Outcomes of annual surveillance imaging in an adult and paediatric cohort of succinate dehydrogenase B mutation carriers

2016 ◽  
Author(s):  
Nicola Tufton ◽  
Lucy Shapiro ◽  
Umasuthan Srirangalingam ◽  
Polly Richards ◽  
Anju Sahdev ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Mutation Carriers ◽  
Surveillance Imaging ◽  
Paediatric Cohort

scholarly journals Tumour risks and genotype–phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD

2018 ◽  
Vol 55 (6) ◽  
pp. 384-394 ◽  
Author(s):  
Katrina A Andrews ◽  
David B Ascher ◽  
Douglas Eduardo Valente Pires ◽  
Daniel R Barnes ◽  
Lindsey Vialard ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Phenotypic Variability ◽  
Cohort Analysis ◽  
Cumulative Risk ◽  
Clinical Information ◽  
Missense Mutations ◽  
Pathogenic Variants ◽  
Mutation Carriers ◽  
Kaplan Meier ◽  
Age Related

BackgroundGermline pathogenic variants in SDHB/SDHC/SDHD are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype–phenotype correlations in a large cohort of SDHB/SDHC/SDHD mutation carriers.MethodsA retrospective survey of 1832 individuals referred for genetic testing due to a personal or family history of phaeochromocytoma/paraganglioma. 876 patients (401 previously reported) had a germline mutation in SDHB/SDHC/SDHD (n=673/43/160). Tumour risks were correlated with in silico structural prediction analyses.ResultsTumour risks analysis provided novel penetrance estimates and genotype–phenotype correlations. In addition to tumour type susceptibility differences for individual genes, we confirmed that the SDHD:p.Pro81Leu mutation has a distinct phenotype and identified increased age-related tumour risks with highly destabilising SDHB missense mutations. By Kaplan-Meier analysis, the penetrance (cumulative risk of clinically apparent tumours) in SDHB and (paternally inherited) SDHD mutation-positive non-probands (n=371/67 with detailed clinical information) by age 60 years was 21.8% (95% CI 15.2% to 27.9%) and 43.2% (95% CI 25.4% to 56.7%), respectively. Risk of malignant disease at age 60 years in non-proband SDHB mutation carriers was 4.2%(95% CI 1.1% to 7.2%). With retrospective cohort analysis to adjust for ascertainment, cumulative tumour risks for SDHB mutation carriers at ages 60 years and 80 years were 23.9% (95% CI 20.9% to 27.4%) and 30.6% (95% CI 26.8% to 34.7%).ConclusionsOverall risks of clinically apparent tumours for SDHB mutation carriers are substantially lower than initially estimated and will improve counselling of affected families. Specific genotype–tumour risk associations provides a basis for novel investigative strategies into succinate dehydrogenase-related mechanisms of tumourigenesis and the development of personalised management for SDHB/SDHC/SDHD mutation carriers.

scholarly journals Clinical Practice Guidance: Surveillance for phaeochromocytoma and paraganglioma in paediatric succinate dehydrogenase gene mutation carriers

2019 ◽  
Vol 90 (4) ◽  
pp. 499-505 ◽  
Author(s):  
Mei Yin Wong ◽  
Katrina A. Andrews ◽  
Benjamin G. Challis ◽  
Soo-Mi Park ◽  
Carlo L. Acerini ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Succinate Dehydrogenase ◽  
Gene Mutation ◽  
Mutation Carriers ◽  
Dehydrogenase Gene

Surveillance of succinate dehydrogenase gene mutation carriers: Insights from a nationwide cohort

2020 ◽  
Vol 92 (6) ◽  
pp. 545-553 ◽  
Author(s):  
Raquel G. Martins ◽  
Nuno Cunha ◽  
Helder Simões ◽  
Maria João Matos ◽  
João Silva ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Gene Mutation ◽  
Mutation Carriers ◽  
Dehydrogenase Gene

scholarly journals Genetic analyses in a cohort of children with pulmonary hypertension

2016 ◽  
Vol 48 (4) ◽  
pp. 1118-1126 ◽  
Author(s):  
Marilyne Levy ◽  
Mélanie Eyries ◽  
Isabelle Szezepanski ◽  
Magalie Ladouceur ◽  
Sophie Nadaud ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Genetic Architecture ◽  
Severe Disease ◽  
Childhood Onset ◽  
First Line ◽  
First Line Therapy ◽  
Mutation Carriers ◽  
Paediatric Cohort ◽  
Pulmonary Arterial ◽  
Index Cases

The prevalence of germline mutations in paediatric pulmonary hypertension (PH) is poorly documented. The objective of this study was to determine the mutation frequency in PH genes in a paediatric cohort and describe the clinical characteristics of mutation carriers.The study involved 66 index cases with PH: 35 children with idiopathic pulmonary arterial hypertension (IPAH); five children with familial PAH (FPAH); three children with pulmonary veno-occlusive disease (PVOD); and 23 children with PAH associated with congenital heart disease (APAH-CHD).No mutations were found in the 23 children with APAH-CHD. In the 40 children with IPAH or FPAH, 12 mutations were found: five on BMPR2; four on ACVRL1; and three on TBX4. In the three PVOD cases, two carried the EIF2AK4 mutation. Mutation carriers had a more severe disease at diagnosis and more aggressive first-line therapy was required. The three patients with PVOD had a very severe disease at diagnosis and required a lung transplantation.The genetic architecture of paediatric PAH is enriched in ACVRL1 and TBX4 mutations compared to adult PAH, but further studies are required to confirm these results. Childhood-onset PAH in children carrying a mutation in one of the genes tested has a more severe presentation at diagnosis but a similar outcome to that observed in non-carriers.

Outcomes of a multicenter surveillance protocol in asymptomatic Succinate Dehydrogenase (SDH) B and C mutation carriers

2021 ◽  
Author(s):  
LLuch Ana R. Romero ◽  
Suset Dueñas Disotuar ◽  
Romero Marai C. Tous ◽  
Peña J. Ignacio Fernández ◽  
Cuenca J. Ignacio Cuenca ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Mutation Carriers ◽  
Surveillance Protocol

Pathoanatomic correlates of psychiatric symptoms in PINK1 mutation carriers

2007 ◽  
Vol 34 (S 2) ◽  
Author(s):  
K Reetz ◽  
R Lencer ◽  
S Steinlechner ◽  
C Gaser ◽  
J Hagenah ◽  
...  
Keyword(s):  
Psychiatric Symptoms ◽  
Mutation Carriers

ACUTE ENZYME HISTOCHEMICAL CHANGES IN THE ZONA GLOMERULOSA OF THE RAT ADRENAL CORTEX

1968 ◽  
Vol 59 (3) ◽  
pp. 508-518
Author(s):  
J. D. Elema ◽  
M. J. Hardonk ◽  
Joh, Koudstaal ◽  
A. Arends
Keyword(s):  
Peritoneal Dialysis ◽  
Succinate Dehydrogenase ◽  
Dehydrogenase Activity ◽  
Adrenal Cortex ◽  
Isocitrate Dehydrogenase ◽  
Hydroxysteroid Dehydrogenase ◽  
Zona Glomerulosa ◽  
Acute Changes ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Histochemical Changes

ABSTRACT Acute changes in glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase activity in the zona glomerulosa of the rat adrenal cortex were induced by peritoneal dialysis with 5 % glucose. Although less clear, the activity of 3β-ol-hydroxysteroid dehydrogenase also seemed to increase as well. No changes were seen in the activity of succinate dehydrogenase. Dialysis with 0.9 % NaCl had no effect on any of the enzymes investigated. The possible significance of these observations is discussed.

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