Prevalence of AIP mutations in a series of Turkish acromegalic patients: are synonymous AIP mutations relevant?

Karaca, Züleyha; Taheri, Serpil; Tanrıverdi, Fatih; Unluhizarci, K.; Keleştimur, Fahrettin

doi:10.1007/s11102-015-0659-0

Cited by 14 publications

(3 citation statements)

References 39 publications

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“…In the FIPA setting, AIP pathogenic variants are demonstrated in about 20% of families, while in cohorts of unselected apparently sporadic pituitary adenomas AIP pathogenic variants are rarely found -in less than 4% (11,84). However, in young adults (diagnosed < 30 years of age) with apparently sporadic adenomas (mostly macroadenomas), the prevalence of AIP pathogenic variants was higher, ranging between 1.6 and 13% (85,86,87,88,89,90,91,92,93). Further decreasing the age of diagnosis (pediatric/ adolescent patients <18 year/old) increases the frequency of AIP pathogenic variants to 11-25% (85,87,94,95,96,97,98).…”

Section: Aip Mutations In Fipa and Sporadic Pituitary Adenomasmentioning

confidence: 99%

Somatic and germline mutations in the pathogenesis of pituitary adenomas

Vandeva

Daly

Pétrossians

et al. 2019

European Journal of Endocrinology

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Pituitary adenomas are frequently occurring neoplasms that produce clinically significant disease in 1:1000 of the general population. The pathogenesis of pituitary tumors is a matter of interest as it could help to improve diagnosis and treatment. Until recently, however, disruptions in relatively few genes were known to predispose to pituitary tumor formation. In the last decade, several more genes and pathways have been described. Germline pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene were found in familial or sporadic pituitary adenomas, usually with an aggressive clinical course. Cyclin-dependent kinase inhibitor 1B (CDKN1B) pathogenic variants lead to multiple endocrine neoplasia type 4 (MEN4) syndrome, in which pituitary adenomas can occur. Xq26.3 duplications involving the gene GPR101 cause X-linked acrogigantism. The pheochomocytoma and/or paraganglioma with pituitary adenoma association (3PAs) syndrome suggests that pathogenic variants in the genes of the succinate dehydrogenase complex or MYC-associated factor X (MAX) might be involved in pituitary tumorigenesis. New recurrent somatic alterations were also discovered in pituitary adenomas, such as, ubiquitin-specific protease 8 (USP8) and USP48 pathogenic variants in corticotropinomas. The aim of the present review is to provide an overview of the genetic pathophysiology of pituitary adenomas and their clinical relevance.

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Section: Aip Mutations In Fipa and Sporadic Pituitary Adenomasmentioning

confidence: 99%

Somatic and germline mutations in the pathogenesis of pituitary adenomas

Vandeva

Daly

Pétrossians

et al. 2019

European Journal of Endocrinology

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“…A pan-European collaboration [ 12 ] analysed a cohort of 163 patients diagnosed with sporadic pituitary macroadenomas before the age of 30 years and reported an 11.7% (19/163) prevalence of AIP mutations. Likewise, other studies carried out in Turkey [ 20 ], Mexico [ 21 ], and Spain [ 22 ], in patients under 30 years, reported prevalences of AIP mutations of 9% (1/11), 7% (5/55), and 6% (9/148), respectively. In contrast, our study showed that only 3.4% (4/118) of Portuguese patients diagnosed under the age of 30 years had AIP mutations.…”

Section: Discussionmentioning

confidence: 61%

Low frequency of AIP mutations in patients with young-onset sporadic pituitary macroadenomas

Gaspar

Gonçalves

Saraiva

et al. 2023

J Endocrinol Invest

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Purpose Mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene cause familial isolated pituitary adenomas (FIPA). AIP mutations have also been found in patients with apparently sporadic pituitary adenomas, particularly in young patients with large adenomas. The aim of this study was to determine the frequency of AIP germline mutations in patients with young-onset sporadic pituitary macroadenomas. Methods The AIP gene was sequenced in 218 Portuguese patients with sporadic pituitary macroadenomas diagnosed before the age of 40 years. Results Heterozygous rare sequence variants in AIP were identified in 18 (8.3%) patients. However, only four (1.8%) patients had pathogenic or likely pathogenic variants. These consisted of two already known mutations (p.Arg81* and p.Leu115Trpfs*41) and two novel mutations (p.Glu246*, p.Ser53Thrfs*36). All four patients had GH-secreting adenomas diagnosed between the ages of 14 and 25 years. The frequency of AIP pathogenic or likely pathogenic variants in patients under the age of 30 and 18 years was 3.4% and 5.0%, respectively. Conclusion The frequency of AIP mutations in this cohort was lower than in other studies. Previous reports may have overestimated the contribution of AIP mutations due to the inclusion of genetic variants of uncertain significance. The identification of novel AIP mutations expands the known spectrum of genetic causes of pituitary adenomas and may help understand the role of AIP mutations in the molecular mechanisms underlying pituitary tumorigenesis.

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“…Disease onset is typically at a younger age in AIP gene variant human acromegalics compared to other causes of acromegaly [10]. AIP-variant acromegaly has also been identified in patients with non-familial human acromegaly [11,12].…”

Section: Introductionmentioning

confidence: 99%