Aberrant Splicing of SDHC in Families With Unexplained Succinate Dehydrogenase-Deficient Paragangliomas

Journal of the Endocrine Society
Sunita M C De SousaDavid J Torpy

Abstract

Germline mutations in the succinate dehydrogenase genes (SDHA/B/C/D, SDHAF2-collectively, "SDHx") have been implicated in paraganglioma (PGL), renal cell carcinoma (RCC), gastrointestinal stromal tumor (GIST), and pituitary adenoma (PA). Negative SDHB tumor staining is indicative of SDH-deficient tumors, usually reflecting an underlying germline SDHx mutation. However, approximately 20% of individuals with SDH-deficient tumors lack an identifiable germline SDHx mutation. We performed whole-exome sequencing (WES) of germline and tumor DNA followed by Sanger sequencing validation, transcriptome analysis, metabolomic studies, and haplotype analysis in 2 Italian-Australian families with SDH-deficient PGLs and various neoplasms, including RCC, GIST, and PA. Germline WES revealed a novel SDHC intronic variant, which had been missed during previous routine testing, in 4 affected siblings of the index family. Transcriptome analysis demonstrated aberrant SDHC splicing, with the retained intronic segment introducing a premature stop codon. WES of available tumors in this family showed chromosome 1 deletion with loss of wild-type SDHC in a PGL and a somatic gain-of-function KIT mutation in a GIST. The SDHC intronic variant identified was ...Continue Reading

References

Feb 22, 2002·American Journal of Medical Genetics·J Aidan Carney, Constantine A Stratakis
May 10, 2002·The New England Journal of Medicine·Hartmut P H NeumannUNKNOWN Freiburg-Warsaw-Columbus Pheochromocytoma Study Group
Mar 23, 2010·The American Journal of Surgical Pathology·Anthony J GillRoderick J Clifton-Bligh
Dec 26, 2012·Frontiers in Oncology·Simon FlanaganMichael E Buckland
Apr 25, 2014·The Journal of Clinical Endocrinology and Metabolism·Tobias ElseVictoria M Raymond
May 27, 2014·Endocrine-related Cancer·Florian HallerAbbas Agaimy
Jun 4, 2014·The Journal of Clinical Endocrinology and Metabolism·Jacques W M LendersWilliam F Young
Jun 24, 2014·Clinical Endocrinology·Juan P BritoMohammad H Murad
Nov 14, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Lucie EvenepoelWinand N M Dinjens
Jan 22, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Heikki JoensuuJean-Francois Emile
Feb 20, 2015·The Journal of Clinical Endocrinology and Metabolism·Paraskevi XekoukiConstantine A Stratakis
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Jul 17, 2015·JAMA Oncology·Samantha HansfordDavid G Huntsman
Aug 11, 2015·The Journal of Clinical Endocrinology and Metabolism·N D NiemeijerE P M Corssmit
Aug 15, 2015·Endocrine-related Cancer·Diana E BennRoderick J Clifton-Bligh
Dec 15, 2015·The Journal of Clinical Endocrinology and Metabolism·Susan RichterGraeme Eisenhofer
Dec 15, 2015·JAMA Oncology·James WhitworthEamonn R Maher
Oct 5, 2016·The Journal of Clinical Endocrinology and Metabolism·Isabelle BourdeauAnne-Paule Gimenez-Roqueplo
Nov 20, 2016·Nature Reviews. Endocrinology·UNKNOWN NGS in PPGL (NGSnPPGL) Study GroupPatricia L M Dahia
Jan 11, 2017·Molecular Genetics and Metabolism Reports·Edward KimRoderick J Clifton-Bligh
May 10, 2017·Endocrine·Emilia SbardellaAshley B Grossman
May 13, 2017·Human Genetics·Rita Vaz-DragoMaria Carmo-Fonseca
May 30, 2017·The Journal of Molecular Diagnostics : JMD·Maria Currás-FreixesMercedes Robledo
Dec 15, 2017·Histopathology·Anthony J Gill
Jul 22, 2018·Journal of the American College of Cardiology·Richard D BagnallChristopher Semsarian
Jul 28, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Susan RichterBarbara Klink
Jan 31, 2019·The Journal of Clinical Endocrinology and Metabolism·Alexandre BuffetUNKNOWN French Group of Endocrine Tumors (GTE) and COMETE Network
Apr 13, 2019·Clinical Genetics·Karin EijkelenkampAnouk N A van der Horst-Schrivers

❮ Previous
Next ❯

Citations

Nov 14, 2021·Endocrine·Sunita M C De SousaRoderick J Clifton-Bligh

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-Seq
PCR
metabolomic profiling

Software Mentioned

STAR
SpliceSiteFinder
Cutadapt
MutationSurveyor
Pyromark Q24
Sequenza
Integrative Genomics Viewer
MaxEntScan
GATK
Ensembl

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
Kaitlin StanleySarangarajan Ranganathan
The Journal of Clinical Endocrinology and Metabolism
Cristóbal Bernardo-CastiñeiraMaría-Dolores Chiara
The Journal of Clinical Endocrinology and Metabolism
Marianne S ElstonAnthony J Gill
© 2021 Meta ULC. All rights reserved