Aryl Hydrocarbon Receptor-Interacting Protein Gene Mutations in Familial Isolated Pituitary Adenomas: Analysis in 73 Families

Daly, Adrian; Vanbellinghen, Jean-François; Khoo, Sok Kean; Jaffrain-Rea, Marie Lise; Naves, Luciana Ansaneli; Guitelman, Mirtha; Murat, A.; Emy, Philippe; Gimenez-Roqueplo, Anne-Paule; Tamburrano, G.; Raverot, Gérald; Barlier, Anne; Herder, Wouter W. de; Penfornis, A.; Ciccarelli, Enrica; Estour, Bruno; Lecomte, P.; Gatta, Blandine; Chabre, Olivier; Sabaté, Maria; Bertagna, Xavier; Basavilbaso, N. García; Stalldecker, Graciela; Colao, Annamaria; Ferollà, Piero; Wémeau, Jean-Louis; Caron, Philippe; Sadoul, Jean‐Louis; Oneto, Adriana; Archambeaud, F.; Calender, Alain; Sinilnikova, Olga M.; Montañana, Carmen Fajardo; Cavagnini, Francesco; Hána, Václav; Solano, Angela; Delettieres, Dreanina; Luccio-Camelo, Douglas C.; Basso, Armando; Rohmer, V.; Brue, Thierry; Bours, Vincent; Teh, Bin Tean; Beckers, Albert

doi:10.1210/jc.2006-2513

Cited by 283 publications

(261 citation statements)

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“…Despite the MEN1-like features of the patients described, studies from Ozawa and colleagues at the NIH and from (24). Despite the advent of mutations in AIP as potential causative features in IFS, the genetic pathophysiology of IFS remains to be fully described as we have found that in 50% of IFS families, no AIP mutations exist (25).…”

Section: Men1mentioning

confidence: 77%

“…Among the FIPA cohort, families with two, three, and four affected members are seen (18,25). FIPA is characterized by a predominance of prolactinomas and GH-secreting tumors, which account for about 75% of the cohort (Fig.…”

Section: Clinical Characteristicsmentioning

confidence: 99%

“…In an international cohort from nine countries, 156 patients comprising 73 FIPA families were included and were classified according to the disease definitions used in earlier studies of the clinical characteristics of FIPA (18,25). A total of 11 out of 73 (15.1%) FIPA families harbored ten different germline AIP mutations, one FIPA family from Italy (unrelated to that reported by Vierimaa et al) had an R304X mutation, and the rest were novel.…”

Section: The Genetics Of Fipamentioning

confidence: 99%

“…The authors would like to acknowledge the invaluable contribution of all physicians at the collaborating centers that provided families with pituitary tumors for the studies described in this review (18,25,39).…”

Section: Acknowledgementsmentioning

confidence: 99%

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The clinical, pathological, and genetic features of familial isolated pituitary adenomas

Beckers¹,

Daly²

2007

eur j endocrinol

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152

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Pituitary adenomas occur in a familial setting in multiple endocrine neoplasia type 1 (MEN1) and Carney's complex (CNC), which occur due to mutations in the genes MEN1 and PRKAR1A respectively. Isolated familial somatotropinoma (IFS) is also a well-described clinical syndrome related only to patients with acrogigantism. Pituitary adenomas of all types -not limited to IFS -can occur in a familial setting in the absence of MEN1 and CNC; this phenotype is termed familial isolated pituitary adenomas (FIPA). Over the past 7 years, we have described over 90 FIPA kindreds. In FIPA, both homogeneous and heterogeneous pituitary adenoma phenotypes can occur within families; virtually all FIPA kindreds contain at least one prolactinoma or somatotropinoma. FIPA differs from MEN1 in terms of a lower proportion of prolactinomas and more frequent somatotropinomas in the FIPA cohort. Patients with FIPA are significantly younger at diagnosis and have significantly larger pituitary adenomas than matched sporadic pituitary adenoma counterparts. A minority of FIPA families overall (15%) exhibit mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene; AIP mutations are present in only half of IFS kindreds occurring as part of the FIPA cohort. In families with AIP mutations, pituitary adenomas have a penetrance of over 50%. AIP mutations are extremely rare in patients with sporadic pituitary adenomas. This review deals with pituitary adenomas that occur in a familial setting, describes in detail the clinical, pathological, and genetic features of FIPA, and addresses aspects of the clinical approach to FIPA families with and without AIP mutations.

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Section: Men1mentioning

confidence: 77%

Section: Clinical Characteristicsmentioning

confidence: 99%

Section: The Genetics Of Fipamentioning

confidence: 99%

Section: Acknowledgementsmentioning

confidence: 99%

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The clinical, pathological, and genetic features of familial isolated pituitary adenomas

Beckers¹,

Daly²

2007

eur j endocrinol

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152

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“…Familial syndromes associated with GH hypersecretion include multiple endocrine neoplasia type 1 (MEN1), in which pituitary, parathyroid, and pancreatic tumors might be associated (4), and the similar MEN4 syndrome caused by germline mutations in the CDKN1B/p27 gene; McCune-Albright syndrome, which involves polyostotic fibrous dysplasia and cutaneous pigmentation (5); and Carney complex, whose clinical picture includes skin pigmentation, mucocutaneous myxomatosis, cardiac myxoma, thyroid and breast lesions (6). Isolated familial acromegaly is described with loss of heterozygosity in chromosome 11q13 (7) and, recently, low-penetrance germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene that were found in individuals who had familial pituitary isolated adenoma (FIPA) predisposition (8)(9)(10).…”

mentioning

confidence: 99%

Genetic studies in a coexistence of acromegaly, pheochromocytoma, gastrointestinal stromal tumor (GIST) and thyroid follicular adenoma

Boguszewski

Fighera

Bornschein

et al. 2012

Arq Bras Endocrinol Metab

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SUMMARYWe report on an adult woman with rare coexistence of acromegaly, pheochromocytoma (PHEO), gastrointestinal stromal tumor (GIST), intestinal polyposis, and thyroid follicular adenoma. At the age of 56, she was diagnosed with acromegaly caused by a pituitary macroadenoma, treated by transsphenoidal surgery, radiotherapy, and octreotide. During routine colonoscopy, multiple polyps were identified as tubular adenomas with high-grade dysplasia on histology. Years later, an abdominal mass of 8.0 x 6.2 cm was detected by routine ultrasound. Surgical exploration revealed an adrenal mass and another tumor adhered to the lesser gastric curvature, which were removed. Pathology confirmed the diagnosis of PHEO and GIST. PHEO immunohistochemistry was negative for GHRH. During follow-up, nodular goiter was found with normal levels of calcitonin and inconclusive cytology. Near-total thyroidectomy was performed, revealing a follicular adenoma. Her family history was negative for all of these tumor types. Genetic analysis for PHEO/paraganglioma genes (SDH A-D, SDHAF2, RET, VHL, TMEM127, and MAX), and pituitary-related genes (AIP, MEN1, and p27) were negative. Though the finding of PHEO and acromegaly with multiple other tumors could be a fortuitous coexistence, we suggest that this case may represent a new variant of MEN syndrome with a de novo germline mutation in a not yet identified gene. Arq Bras Endocrinol Metab. 2012;56(8):507-12 SUMÁRIORelatamos o caso de uma mulher com rara coexistência de acromegalia, feocromocitoma (FEO), tumor do estroma gastrointestinal (GIST), polipose intestinal e adenoma folicular de tireoide. Aos 56 anos, ela foi diagnosticada com acromegalia por um macroadenoma hipofisário, tratado com cirurgia transesfenoidal, radioterapia e octreotide. Uma colonoscopia de rotina detectou múltiplos pólipos, que à histologia eram adenomas tubulares com alto grau de displasia. Anos mais tarde, uma ecografia detectou uma massa abdominal de 8.0 x 6.2 cm, que na exploração cirúrgica era uma lesão adrenal e outro tumor aderido à pequena curvatura gás-trica. A patologia confirmou os diagnósticos de FEO e GIST. A imuno-histoquímica do FEO foi negativa para GHRH. No seguimento, encontrou-se um bócio nodular com níveis normais de calcitonina e citologia inconclusiva. Após tireoidectomia total o diagnóstico histológico foi de adenoma folicular. A história familiar era negativa para todos esses tumores. As análises gené-ticas para genes de síndromes de FEO/paragangliomas (SDH A-D, SDHAF2, RET, VHL, TMEM127 e MAX) e para hipofisárias (AIP, MEN1 e p27) foram todas negativas. Embora a presença de FEO e acromegalia com múltiplos outros tumores possa ser uma coexistência fortuita, acreditamos na possibilidade de uma nova variante de NEM com uma mutação germinativa de novo em um gene ainda não identificado Arq Bras Endocrinol Metab. 2012;56(8):507-12

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Familial Pituitary Adenomas

Hernández-Ramírez

Korbonits

2013

Pituitary Disorders

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Aryl Hydrocarbon Receptor-Interacting Protein Gene Mutations in Familial Isolated Pituitary Adenomas: Analysis in 73 Families

Cited by 283 publications

References 22 publications

The clinical, pathological, and genetic features of familial isolated pituitary adenomas

The clinical, pathological, and genetic features of familial isolated pituitary adenomas

Genetic studies in a coexistence of acromegaly, pheochromocytoma, gastrointestinal stromal tumor (GIST) and thyroid follicular adenoma

Familial Pituitary Adenomas

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