Abstract Search

ea0065oc5.5 | Adrenal and Cardiovascular | SFEBES2019

Somatic transmembrane domain mutations of a cell adhesion molecule, CADM1, cause primary aldosteronism by preventing gap junction communication between adrenocortical cells

Wu Xilin , Garg Sumedha , Cabrera Claudia , Azizan Elena , Zhou Junhua , Mein Chaz , Takaoka Yutaka , Wozniak Eva , Zhao Wanfeng , Marker Alison , Buss Folma , Murakami Masanori , Beuschlein Felix , Reincke Martin , Ito Akihiko , Brown Morris

Background: Primary Aldosteronism (PA) is the commonest curable cause of hypertension. Whole exome sequencing (WES) of an aldosterone producing adenoma from a 46-year-old man with resistant hypertension revealed a novel somatic mutation (Val380Asp) of the single transmembrane domain of Cell Adhesion Molecule-1 (CADM1). A Gly379Asp mutation was identified by WES of a PA patient in Munich. Both patients were cured of hypertension by adrenalectomy.Method: A...

0 shares

ea0063gp94 | Adrenal and Neuroendocrine - Basic | ECE2019

Somatic transmembrane domain mutations of a cell adhesion molecule, CADM1, cause primary aldosteronism by preventing gap junction communication between adrenocortical cells

Wu Xilin , Garg Sumedha , Cabrera Claudia , Azizan Elena , Mein Chaz , Takaoka Yutaka , Wozniak Eva , Zhao Wanfeng , Marker Alison , Buss Folma , Murakami Masanori , Beuschlein Felix , Reincke Martin , Ito Akihiko , Brown Morris

Background: PA is the commonest curable cause of hypertension. Whole exome sequencing (WES) in 2011 and 2013 identified common somatic mutations in genes regulating membrane polarisation in 60-80% of aldosterone-producing adenomas (APA). In search of the missing variants, we undertook further WES. One APA from a 46-year-old gentleman revealed a novel somatic mutation (Val380Asp); which introduced a charged amino-acid into the single transmembrane domain of Cell Adhesion Molecu...

0 shares

ea0077oc4.2 | Adrenal and Cardiovascular | SFEBES2021

Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.

Argentesi Giulia , Azizan Elena , Zhou Junhua , Cabrera Claudia , O’Toole Sam , Wu Xilin , Goodchild Emily , Cottrell Emily , Marker Alison , Senanayake Russell , Garg Sumedha , Jordan Suzanne , Berney Dan , Gluck Anna , Lines Kate , Thakker Rajesh V , Tuthill Antoinette , Joyce Caroline , Karet Frankl Fiona , Metherell Lou , Teo Ada , Gurnell Mark , Parvanta Laila , Drake William , Wozniak Eva , Mein Chaz , Kinsler Veronika , Storr Helen , Brown Morris

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell-clusters of normal adrenals could suggest the existence of co-driver mutations which influence the development or phenotype of APAs [1]. Gain-of-function mutations in both CTNNB1 and the G-protein coupled receptor GNA11 were found by whole exome sequencing in 3/10 APAs. Further sequencing of...

0 shares

ea0086op2.3 | Adrenal and Cardiovascular | SFEBES2022

Complete clinical cure of primary aldosteronism (PA) is predictable and sustained for at least two years

Goodchild Emily , Wu Xilin , Senanayake Russell , Bashari Waiel , Salsbury Jackie , Cabrera Claudia , Argentesi Giulia , O'Toole Samuel , MacFarlane James , Laycock Kate , Benu Daniela , Matson Matthew , Koo Brendan , Parvanta Laila , Hilliard Nick , Kosmoliaptsis Vasilis , Marker Alison , Berney Daniel , Tan Wilson , Foo Roger , Mein Charles , Wozniak Eva , Savage Emmanuel , Sahdev Anju , Bird Nicholas , Boros Istvan , Hader Stefan , Warnes Victoria , Gillett Dan , Dawnay Anne , Adeyeye Elizabeth , Prete Alessandro , Taylor Angela , Wiebke Arlt , Bhuva Anish , Aigbirhio Franklin , Manisty Charlotte , Cruickshank Kennedy , Cheow Heok , Gurnell Mark , Drake William , Brown Morris

Introduction: In a prospective within-patient study (MATCH) 11C-metomidate PET-CT (MTO) was an accurate non-invasive alternative to adrenal vein sampling in the detection of unilateral PA1. Post-adrenalectomy (ADX), 24/78 (30%) patients achieved complete clinical success (PASO consensus) at 6 months, but 75% achieved reduction in B-type natriuretic peptide (BNP).Aim: To determine: 1. the number of patients who sustain complete clinical success...

0 shares

Endocrine Abstracts

Somatic transmembrane domain mutations of a cell adhesion molecule, CADM1, cause primary aldosteronism by preventing gap junction communication between adrenocortical cells

Somatic transmembrane domain mutations of a cell adhesion molecule, CADM1, cause primary aldosteronism by preventing gap junction communication between adrenocortical cells

Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.

Complete clinical cure of primary aldosteronism (PA) is predictable and sustained for at least two years

BiosciAbstracts