An analysis of surveillance screening for SDHB-related disease in childhood and adolescence.

Objective Phaeochromocytomas (PCC) and paragangliomas (PGL) are rare in children. A large proportion of these are now understood to be due to underlying germline mutations. Here we focus on succinate dehydrogenase subunit B (SDHB) gene mutation carriers as these tumours carry a high risk of malignant transformation.

Emergence of Pituitary Adenoma in a Child during Surveillance: Clinical Challenges and the Family Members' View in an Mutation-Positive Family.

Introduction: Germline aryl hydrocarbon receptor-interacting protein () mutations are responsible for 15-30% of familial isolated pituitary adenomas (FIPAs). We report a FIPA kindred with a heterozygous deletion in , aiming to highlight the indications and benefits of genetic screening, variability in clinical presentations, and management challenges in this setting.

Patients: An 18-year-old male was diagnosed with a clinically nonfunctioning pituitary adenoma (NFPA).

Clinical and molecular characterization of -related severe early-onset epilepsy.

Objective: To characterize the phenotypic spectrum, molecular genetic findings, and functional consequences of pathogenic variants in early-onset epilepsy.

Methods: We identified a cohort of 31 patients with epilepsy of infancy with migrating focal seizures (EIMFS) and screened for variants in using direct Sanger sequencing, a multiple-gene next-generation sequencing panel, and whole-exome sequencing. Additional patients with non-EIMFS early-onset epilepsy in whom we identified variants on local diagnostic multiple gene panel testing were also included.

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

Objective: For 'asymptomatic carriers' of the succinate dehydrogenase subunit B (SDHB) gene mutations, there is currently no consensus as to the appropriate modality or frequency of surveillance imaging. We present the results of a surveillance programme of SDHB mutation carriers.

Design: Review of clinical outcomes of a surveillance regimen in patients identified to have an SDHB gene mutation, based on annual MRI, in a single UK tertiary referral centre.

Increased Population Risk of AIP-Related Acromegaly and Gigantism in Ireland.

The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304 (or p.R304 ; NM_003977.3:c.

Mitral Stenosis, LV Aneurysm, Myocardial Bridge, and Myocardial Infarction: The Mystery Demystified.

Coronary embolisation, spontaneous coronary artery dissection, and myocardial bridges are rare causes of Myocardial Infarction (MI) in the youth. Here, we report a young male who developed myocardial infarction at the age of 19. Investigations revealed that he had mitral stenosis, myocardial bridge, and angiographic features of healed coronary dissection.

Clinical experience in the screening and management of a large kindred with familial isolated pituitary adenoma due to an aryl hydrocarbon receptor interacting protein (AIP) mutation.

Context: Germline AIP mutations usually cause young-onset acromegaly with low penetrance in a subset of familial isolated pituitary adenoma families. We describe our experience with a large family with R304* AIP mutation and discuss some of the diagnostic dilemmas and management issues.

Objective: The aim of the study was to identify and screen mutation carriers in the family.

A comprehensive next generation sequencing-based genetic testing strategy to improve diagnosis of inherited pheochromocytoma and paraganglioma.

Context: Pheochromocytomas and paragangliomas are notable for a high frequency of inherited cases, many of which present as apparently sporadic tumors.

Objective: The objective of this study was to establish a comprehensive next generation sequencing (NGS)-based strategy for the diagnosis of patients with pheochromocytoma and paraganglioma by testing simultaneously for mutations in MAX, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and VHL.

Design: After the methodology for the assay was designed and established, it was validated on DNA samples with known genotype and then patients were studied prospectively.

Evaluation of SDHB, SDHD and VHL gene susceptibility testing in the assessment of individuals with non-syndromic phaeochromocytoma, paraganglioma and head and neck paraganglioma.

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.

Familial pituitary adenomas - who should be tested for AIP mutations?

Familial Isolated Pituitary Adenomas (FIPA), an autosomal dominant disease with low penetrance is being increasingly recognized. FIPA families can be divided into two distinct groups based on genetic and phenotypic features. Patients with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are characterized by young-onset somatotroph or lactotroph macroadenomas, while in the other, larger group of FIPA patients with typically adult-onset disease and more varied adenoma types, no causative gene(s) has been identified.

AIP mutation in pituitary adenomas in the 18th century and today.

Gigantism results when a growth hormone-secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783, he noted an enlarged pituitary fossa. We extracted DNA from the patient's teeth and identified a germline mutation in the aryl hydrocarbon-interacting protein gene (AIP).

Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families.

Familial isolated pituitary adenoma (FIPA) is an autosomal dominant condition with variable genetic background and incomplete penetrance. Germline mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene have been reported in 15-40% of FIPA patients. Limited data are available on the functional consequences of the mutations or regarding the regulation of the AIP gene.

A novel protein that binds to dnrN-dnrO intergenic region of Streptomyces peucetius purified by DNA affinity capture has dihydrolipoamide dehydrogenase activity.

An antitumour chemotherapeutic, daunorubicin (DNR), produced by Streptomyces peucetius exhibits cytotoxic activity through topoisomerase-mediated interaction with DNA, thereby inhibiting DNA replication and repair and RNA and protein synthesis. It is synthesized by the type II polyketide pathway. Understanding molecular mechanisms that drive expression of antibiotic biosynthetic genes in response to diverse signals and chemical inducers is of considerable interest.

Large genomic deletions in AIP in pituitary adenoma predisposition.

Context: Germline mutations in AIP have been recently shown to cause pituitary adenoma predisposition (PAP). Subsequently, many intragenic germline mutations have been reported, both in familial and in sporadic settings.

Objective: Our objective was to evaluate the possible contribution of large genomic germline AIP deletions, an important mutation type in tumor predisposition syndromes, in PAP.