Succinate dehydrogenase gene mutations are strongly associated with paraganglioma of the organ of Zuckerkandl

Organ of Zuckerkandl paragangliomas (PGLs) are rare neuroendocrine tumors that are derived from chromaffin cells located around the origin of the inferior mesenteric artery extending to the level of the aortic bifurcation. Mutations in the genes encoding succinate dehydrogenase subunits (SDH) B, C, and D (SDHx) have been associated with PGLs, but their contribution to PGLs of the organ of Zuckerkandl PGLs is not known. We aimed to describe the clinical presentation of patients with PGLs of the organ of Zuckerkandl and investigate the prevalence of SDHx mutations and other genetic defects among them. The clinical characteristics of 14 patients with PGL of the organ of Zuckerkandl were analyzed retrospectively; their DNA was tested for SDHx mutations and deletions. Eleven out of 14 (79%) patients with PGLs of the organ of Zuckerkandl were found to have mutations in the SDHB (9) or SDHD (2) genes; one patient was found to have the Carney–Stratakis syndrome (CSS), and his PGL was discovered during surgery for gastrointestinal stromal tumor. Our results show that SDHx mutations are prevalent in pediatric and adult PGLs of the organ of Zuckerkandl. Patients with PGLs of the organ of Zuckerkandl should be screened for SDHx mutations and the CSS; in addition, asymptomatic carriers of an SDHx mutation among the relatives of affected patients may benefit from tumor screening for early PGL detection.

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Analysis of genetic and clinical characteristics of a Chinese Kallmann syndrome cohort with ANOS1 mutations

Acta Endocrinologica ◽

10.1530/eje-17-0335 ◽

2017 ◽

Vol 177 (4) ◽

pp. 389-398 ◽

Cited By ~ 7

Author(s):

Min Nie ◽

Hongli Xu ◽

Rongrong Chen ◽

Jiangfeng Mao ◽

Xi Wang ◽

...

Keyword(s):

Clinical Characteristics ◽

Clinical Presentation ◽

Direct Sequencing ◽

Gene Mutations ◽

Kallmann Syndrome ◽

Chinese Patients ◽

Missense Mutations ◽

The Novel ◽

Novel Mutations ◽

Functional Relevance

Objective To analyze ANOS1 gene mutations in a large Chinese Kallmann syndrome (KS) cohort and to characterize the clinical presentation of the disease in patients with ANOS1 mutations. Patients and methods Chinese patients with KS, including 187 sporadic and 23 pedigree cases were recruited. Patients’ ANOS1 gene sequences were analyzed by direct sequencing of PCR-amplified products. In silico analysis was used to assess functional relevance of newly identified missense mutations. Patients’ clinical characteristics were analyzed retrospectively. Result(s) Fifteen nonsynonymous rare ANOS1 variants were found in 13 out of 187 sporadic and 8 out of 23 familial IHH probands. Seven novel (C86F, C90Y, C151W, Y379X, c.1062 + 1G > A, Y579L fs 591X, R597X) and eight recurrent ANOS1 mutations (S38X, R257X, R262X, R423X, R424X, V560I, c.1843-1G > A, p.R631X) were identified. All the novel mutations were predicted to be pathogenic. The prevalence of cryptorchidism was high (38.1%) and occurred in patients with different kind of ANOS1 mutations, while the patients with the same mutation did not present with cryptorchidism uniformly. Conclusion(s) The prevalence of ANOS1 gene mutations is low in sporadic KS patients, but is much higher in familial KS patients. In the present study, we identify seven novel ANOS1 mutations, including two mutations in the CR domain, which are probably pathogenic. These mutations expand the ANOS1 mutation spectrum and provide a foundation for prenatal diagnosis and genetic counseling.

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Adrenocortical carcinoma and succinate dehydrogenase gene mutations: an observational case series

Acta Endocrinologica ◽

10.1530/eje-17-0358 ◽

2017 ◽

Vol 177 (5) ◽

pp. 439-444 ◽

Cited By ~ 12

Author(s):

Tobias Else ◽

Antonio Marcondes Lerario ◽

Jessica Everett ◽

Lori Haymon ◽

Deborah Wham ◽

...

Keyword(s):

Succinate Dehydrogenase ◽

Loss Of Heterozygosity ◽

Adrenocortical Carcinoma ◽

Cushing Syndrome ◽

Case Series ◽

Gene Mutations ◽

Loss Of Function ◽

Dehydrogenase Gene ◽

Rare Manifestation ◽

Adrenal Masses

Objective Germline loss-of-function mutations in succinate dehydrogenase (SDHx) genes results in rare tumor syndromes that include pheochromocytoma, paraganglioma, and others. Here we report a case series of patients with adrenocortical carcinoma (ACC) that harbor SDHx mutations. Patients and results We report four unrelated patients with ACC and SDHx mutations. All cases presented with Cushing syndrome and large adrenal masses that were confirmed to be ACC on pathology. All four ACC specimens were found to have truncating mutations in either SDHC or SDHA, while cases 1, 2 and 3 also had the mutations confirmed in the germline: Case 1: SDHC c.397C > T, pR133X; Case 2: SDHC c.43C > T, p.R15X; Case 3: SDHA c.91C > T, p.R31X; Case 4: SDHA c.1258C > T, p.Q420X. Notably, Case 1 had a father and daughter who both harbored the same SDHC germline mutation, and the father had a paraganglioma and renal cell carcinoma. A combination of next generation sequencing, and/or immunohistochemistry, and/or mass spectroscopy was used to determine whether there was loss of heterozygosity and/or loss of SDH protein expression or function within the ACC. Potential evidence of loss of heterozygosity was observed only in Case 2. Conclusions We observed truncating mutations in SDHA or SDHC in the ACC and/or germline of four unrelated patients. Given how statistically improbable the concurrence of ACC and pathogenic germline SDHx mutations is expected to be, these observations raise the question whether ACC may be a rare manifestation of SDHx mutation syndromes. Further studies are needed to investigate the possible role of SDH deficiency in ACC pathogenesis.

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A review of the tumour spectrum of germline succinate dehydrogenase gene mutations: Beyond phaeochromocytoma and paraganglioma

Clinical Endocrinology ◽

10.1111/cen.14289 ◽

2020 ◽

Vol 93 (5) ◽

pp. 528-538 ◽

Cited By ~ 2

Author(s):

James MacFarlane ◽

Keat Cheah Seong ◽

Chad Bisambar ◽

Basetti Madhu ◽

Kieren Allinson ◽

...

Keyword(s):

Succinate Dehydrogenase ◽

Gene Mutations ◽

Dehydrogenase Gene ◽

Tumour Spectrum

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Succinate Dehydrogenase Gene Mutations in Cardiac Paragangliomas

The American Journal of Cardiology ◽

10.1016/j.amjcard.2015.03.020 ◽

2015 ◽

Vol 115 (12) ◽

pp. 1753-1759 ◽

Cited By ~ 15

Author(s):

Victoria L. Martucci ◽

Abbas Emaminia ◽

Jaydira del Rivero ◽

Ronald M. Lechan ◽

Bindiya T. Magoon ◽

...

Keyword(s):

Succinate Dehydrogenase ◽

Gene Mutations ◽

Dehydrogenase Gene

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Mediastinal paragangliomas: association with mutations in the succinate dehydrogenase genes and aggressive behavior

Endocrine Related Cancer ◽

10.1677/erc-08-0214 ◽

2009 ◽

Vol 16 (1) ◽

pp. 291-299 ◽

Cited By ~ 26

Author(s):

Hans K Ghayee ◽

Bas Havekes ◽

Eleonora P M Corssmit ◽

Graeme Eisenhofer ◽

Stephen R Hammes ◽

...

Keyword(s):

Aggressive Behavior ◽

Succinate Dehydrogenase ◽

Germ Line ◽

Abdominal Mass ◽

Gene Mutations ◽

Genetic Alterations ◽

Clinical Behavior ◽

Presenting Symptoms ◽

Catecholamine Excess ◽

Genes Encoding

Extra-adrenal pheochromocytomas, otherwise known as paragangliomas (PGLs), account for about 20% of catecholamine-producing tumors. Catecholamine excess and mutations in the genes encoding succinate dehydrogenase subunits (SDHx) are frequently found in patients with PGLs. Only 2% of PGLs are found in the mediastinum, and little is known about genetic alterations in patients with mediastinal PGLs, catecholamine production by these tumors, or their clinical behavior. We hypothesized that most mediastinal PGLs are associated with germ line SDHx mutations, norepinephrine and/or dopamine excess, and aggressive behavior. The objective of this study was to characterize genetic, biochemical, and clinical data in a series of ten patients with mediastinal PGLs. All ten primary mediastinal PGL patients had germ line SDHx mutations, six in SDHB, and four in SDHD genes. Chest or back pain were the most common presenting symptoms (five patients), and catecholamines and/or their metabolites were elevated in seven patients. Additional tumors included head and neck PGLs in four patients, pheochromocytoma in one patient, and bladder PGL in another. Metastatic disease was documented in six patients (60%), and a concurrent abdominal mass was found in one patient. We conclude that mediastinal PGLs are strongly associated with SDHB and SDHD gene mutations, noradrenergic phenotype, and aggressive behavior. The present data suggest that all patients with mediastinal PGLs should be screened for SDHx gene mutations, regardless of age.

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SDHB and SDHA Immunohistochemistry in Canine Pheochromocytomas

Animals ◽

10.3390/ani10091683 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1683

Author(s):

Firas M. Abed ◽

Melissa A. Brown ◽

Omar A. Al-Mahmood ◽

Michael J. Dark

Keyword(s):

Succinate Dehydrogenase ◽

Chromaffin Cells ◽

Genetic Basis ◽

Adrenal Glands ◽

Gene Mutations ◽

High Rate ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Highly Correlated ◽

Formalin Fixed

Pheochromocytomas (PCs) are tumors arising from the chromaffin cells of the adrenal glands and are the most common tumors of the adrenal medulla in animals. In people, these are highly correlated to inherited gene mutations in the succinate dehydrogenase (SDH) pathway; however, to date, little work has been done on the genetic basis of these tumors in animals. In humans, immunohistochemistry has proven valuable as a screening technique for SDH mutations. Human PCs that lack succinate dehydrogenase B (SDHB) immunoreactivity have a high rate of mutation in the SDH family of genes, while human PCs lacking succinate dehydrogenase A (SDHA) immunoreactivity have mutations in the SDHA gene. To determine if these results are similar for dogs, we performed SDHA and SDHB immunohistochemistry on 35 canine formalin-fixed, paraffin-embedded (FFPE) PCs. Interestingly, there was a loss of immunoreactivity for both SDHA and SDHB in four samples (11%), suggesting a mutation in SDHx including SDHA. An additional 25 (71%) lacked immunoreactivity for SDHB, while retaining SDHA immunoreactivity. These data suggest that 29 out of the 35 (82%) may have an SDH family mutation other than SDHA. Further work is needed to determine if canine SDH immunohistochemistry on PCs correlates to genetic mutations that are similar to human PCs.

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Multiple Right and Left Pulmonary Arteries and Subdivisions of Inferior Mesenteric Artery Aneurysms in Behcet’s Disease Case: A Rare Clinical Presentation

Oman Medical Journal ◽

10.5001/omj.2014.63 ◽

2014 ◽

Vol 29 (3) ◽

Cited By ~ 1

Author(s):

Reza Faridhosseini ◽

Farah Jabbari ◽

Afshin Shirkani ◽

Mohammad Reza Zandkarimi ◽

Hadis Yousefzadeh ◽

...

Keyword(s):

Behçet’S Disease ◽

Mesenteric Artery ◽

Inferior Mesenteric Artery ◽

Behcet’S Disease ◽

Clinical Presentation ◽

Behçet's Disease ◽

Pulmonary Arteries ◽

Behcet's Disease ◽

Disease Case

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Hydrocephalus in Spinal Muscular Atrophy: A Case Report and Review of the Literature

Journal of Pediatric Neurology ◽

10.1055/s-0040-1721131 ◽

2020 ◽

Author(s):

Jeetendra P. Sah ◽

Aaron W. Abrams ◽

Geetha Chari ◽

Craig Linden ◽

Yaacov Anziska

Keyword(s):

Spinal Muscular Atrophy ◽

Clinical Characteristics ◽

Clinical Presentation ◽

Muscular Atrophy ◽

Communicating Hydrocephalus ◽

Type I ◽

Review Of The Literature ◽

Radiographic Findings ◽

Comprehensive Review ◽

The Relationship

AbstractIn this article, we reported a case of spinal muscular atrophy (SMA) type I noted to have tetraventricular hydrocephalus with Blake's pouch cyst at 8 months of age following intrathecal nusinersen therapy. The association of hydrocephalus with SMA is rarely reported in the literature. Development of hydrocephalus after intrathecal nusinersen therapy is also reported in some cases, but a cause–effect relationship is not yet established. The aim of this study was to describe the clinical characteristics of a patient with SMA type I and hydrocephalus, to review similar cases reported in the literature, and to explore the relationship between nusinersen therapy and development of hydrocephalus. The clinical presentation and radiographic findings of the patient are described and a comprehensive review of the literature was conducted. The adverse effect of communicating hydrocephalus related to nusinersen therapy is being reported and the authors suggest carefully monitoring for features of hydrocephalus developing during the course of nusinersen therapy.

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Image-guided translumbar type II endoleak repair: A novel approach

American Journal of Interventional Radiology ◽

10.25259/ajir_6_2019 ◽

2020 ◽

Vol 4 ◽

pp. 9

Author(s):

Salman Mirza ◽

Shahnawaz Ansari

Keyword(s):

Mesenteric Artery ◽

Inferior Mesenteric Artery ◽

Endovascular Aneurysm Repair ◽

Type Ii ◽

Type Ii Endoleak ◽

Image Guided ◽

Novel Approach ◽

Abdominal Aortic ◽

Aneurysm Repair

We present a case of a 72-year-old male with an abdominal aortic aneurysm status post-endovascular aneurysm repair (EVAR). Follow-up imaging demonstrated an enlarging type II endoleak and attempts at transarterial coil embolization of the inferior mesenteric artery were unsuccessful. The patient underwent image-guided percutaneous translumbar type II endoleak repair using XperGuide (Philips, Andover, MA USA).

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