Searchable abstracts of presentations at key conferences in endocrinology

ea0050oc5.6 | Reproduction and Neuroendocrinology | SFEBES2017

The MAPK effector B-Raf is essential for hypothalamic–pituitary axis development and activating mutations in BRAF cause congenital hypopituitarism

Kyprianou Nikolina , Gregory Louise , Lillina Vignola Maria , Besser Rachel , Marinelli Eugenia , Gualtieri Angelica , Scagliotti Valeria , Davis Shannon , Gevers Evelien , Dattani Mehul , Gaston-Massuet Carles

Somatic activating mutations in BRAF, encoding B-Raf, have been described in tumours and recently craniopharyngiomas. Germline mutations in BRAF and other components of the RAS/MAPK pathway are found in RASopathies, whose features include endocrine deficiencies but not craniopharyngiomas. We report three BRAF mutations (two of which are novel) in four children with congenital hypopituitarism. To demonstrate the functional role of the three variants w...

ea0050p273 | Neuroendocrinology and Pituitary | SFEBES2017

Cyclooxygenase-2 is a potential target for the treatment of Adamantinomatous craniopharyngioma

Scagliotti Valeria , Gutierrez Lorena Perez , Gualtieri Angelica , Jimenez Fernando , Kirkby Nicholas , Mitchell Jane , Warner Timothy , Gevers Evelien , Dattani Mehul , Gaston-Massuet Carles

Adamantinomatous craniopharyngiomas (ACPs) are among the most common intracranial tumours in children and they originate from undifferentiated pituitary progenitors. Mutations in the gene encoding for β-catenin (CTNNB1), which lead to the constitutive activation of the Wnt/β-catenin signalling pathway, have been associated with ACP. These tumours can invade adjacent structures, such as the hypothalamus, which makes comp...

ea0058p028 | Miscellaneous Endocrinology | BSPED2018

A 10 year experience of the management of severe hypocalcaemia associated with thymus transplantation in a United Kingdom tertiary centre

Goff Nicole , Katugampola Harshini , Monti Elena , Taylor Katherine , Amin Rakesh , Hindmarsh Peter , Peters Catherine , Shah Pratik , Spoudeas Helen , Dattani Mehul , Allgrove Jeremy , Brain Caroline

Background: Thymus transplantation is undertaken for conditions associated with severe immunodeficiency. These comprise various genetic and syndromic associations including 22q deletion syndrome, CHARGE association, diabetic embryopathy, and other rarer conditions. Some of these conditions are associated with hypoparathyroidism and therefore hypocalcaemia. There are no established guidelines on the management and prevention of hypocalcaemia during the transplant period.<p ...

ea0034p398 | Thyroid | SFEBES2014

Neurocognitive and CNS abnormalities in humans with defective thyroid receptor α

Moran Carla , Visser Edward , Schoenmakers Nadia , Muntoni Francesco , Clark Chris , Gadian David , Chong Kling , Kuczynski Adam , Dattani Mehul , Vargha-Khadem Faraneh , Chatterjee Krishna

Background: The severe neurodevelopmental phenotype of untreated congenital hypothyroidism exemplifies the critical role of thyroid hormones (TH) in CNS development, acting via thyroid hormone receptor α1 (TRα1) on cortical neurogenesis, cerebellar development and oligodendrocyte differentiation. We have identified the first humans with defective TRα1 and investigated neurocognitive phenotype and CNS abnormalities in this disorder.Methods:...

ea0031yep1.2 | Young endocrinologists' prize lectures | SFEBES2013

The Wnt/β-catenin effector Tcf3/TCF7L1 is required for normal hypothalamic–pituitary development

Gaston-Massuet Carles , McCabe Mark , Wu Chun-I , Gharavy S. Neda Mousavy , Koniordou Markella , Merrill Bradley J , Dattani Mehul , Martinez-Barbera Juan Pedro

The pituitary gland, is a small midline organ situated at the base of the brain, that acts as a master regulator of multiple physiological functions: such as growth, puberty, metabolism, stress response, reproduction and lactation. The pituitary gland is composed of three lobes: the anterior and intermediate, which form the anterior pituitary (AP and contains hormone producing cells), and the posterior lobe which constitutes the posterior pituitary (PP contains axonal inputs)....

ea0030oc1.6 | Oral Communications 1 | BSPED2012

A novel syndrome characterized by hypothalamic hormonal insufficiency, neonatal seizures, congenital abnormalities of the kidneys and urinary tract and obesity due to mutation in a gene regulating hypothalamic development

Webb Emma , Kelberman Dan , Mutair Angham Al , Andoniadou Cynthia , Bacchelli Chiara , Chanudet Estelle , Kleta Robert , Lescai F , Stupka E , Beales P , Sowden Jane , Martinez JP , Dattani Mehul

Introduction: Mutations affecting hypothalamic development in humans have been identified in genes that affect isolated domains of hypothalamic function leading to restricted phenotypes, such as obesity or hypogonadotrophic hypogonadism. We describe the first human cases of diabetes insipidus and combined pituitary hormone deficiency due to a mutation in a gene regulating hypothalamic development.Results: Six affected individuals from a highly consanguin...

ea0027oc1.8 | Oral Communications 1 | BSPED2011

Mutations in PROKR2 but not PROK2 are associated with congenital hypopituitarism and septo-optic dysplasia

McCabe Mark , Gregory Louise , Gaston-Massuet Carles , Sbai Oualid , Rondard Philippe , Pfeifer Marija , Hulse Tony , Buchanan Charles , Pitteloud Nelly , Martinez-Barbera Juan-Pedro , Dattani Mehul

Introduction: Loss-of-function mutations in PROK2 and PROKR2 in humans have been associated with Kallmann syndrome (KS), characterised by the combination of hypogonadotrophic hypogonadism with anosmia, suggesting that both are critical for GnRH neuronal development.Objective: KS has overlapping phenotypes and genotypes through FGF8 and FGFR1 with congenital hypopituitarism including septo-optic dysplasia (SOD) and thus we aime...

ea0027oc2.8 | Oral Communications 2 (Quick Fire) | BSPED2011

Novel SOX2 mutation: from clinical phenotype to identification of new molecular mechanisms of SOX2 action and interactions

Alatzoglou Kyriaki S , Andoniadou Cynthia L , Kelberman Daniel , Kim Hyoong-Goo , Pedersen-White Jennifer , Layman Lawrence , Martinez-Barbera Juan Pedro , Dattani Mehul T

Background: SOX2 is an early developmental transcription factor implicated in pituitary development. It consists of a N-terminal domain, a high mobility group (HMG)-DNA binding domain and a carboxyl-terminal domain. Heterozygous SOX2 mutations have been described in patients with a severe ocular phenotype and hypogonadotrophic hypogonadism (HH) with/without associated abnormalities. In vitro SOX2 interacts with β-catenin, a member of the Wnt signalling pathway, and...

ea0021p231 | Growth and development | SFEBES2009

Phenotypic presentation of P450 oxidoreductase deficiency during puberty

Idkowiak Jan , O'Riordan Stephen , Reisch Nicole , Dhir Vivek , Malunowicz Ewa , Kerstens Michiel , Maiter Dominique , Collines Felicity , Silink Martin , Dattani Mehul , Shackleton Cedric , Krone Nils , Arlt Wiebke

P450 oxidoreductase (POR) transfers electrons to all microsomal P450 enzymes including CYP21A2 and CYP17A1, key enzymes of glucocorticoid and andogen synthesis, respectively. Mutant POR results P450 oxidoreductase deficiency (ORD) manifesting with glucocorticoid deficiency and disordered sex development in both sexes. Neonatal presentation with undervirilisation in boys and virilisation in girls is well described. However, there is a paucity of data on the pubertal phenotype i...

ea0013oc16 | Young Endocrinologist prize session | SFEBES2007

Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) cause 46,XY disorders of sex development with normal adrenal function

Lin Lin , Philibert Pascal , Ferraz-de-Souza Bruno , Kelberman Daniel , Homfray Tessa , Albanese Assunta , Molini Veruska , Sebire Neil , Einaudi Silvia , Jameson Larry , Sultan Charles , Dattani Mehul , Achermann John

The nuclear receptor steroidogenic factor 1 (SF1/AdBP4/FTZF1, NR5A1) is a key regulator of adrenal and gonadal development, steroidogenesis and reproduction, and targeted deletion of Nr5a1 (Sf1) in the mouse results in adrenal and gonadal agenesis, XY sex-reversal and persistent Müllerian structures in males. Consistent with this phenotype, DNA-binding mutations in SF1 have been reported in two 46,XY female patients with primary adrenal failure and uterine s...