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Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study

Overview of attention for article published in Acta Neuropathologica Communications, June 2016
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Title
Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study
Published in
Acta Neuropathologica Communications, June 2016
DOI 10.1186/s40478-016-0328-1
Pubmed ID
Authors

Donato Iacovazzo, Richard Caswell, Benjamin Bunce, Sian Jose, Bo Yuan, Laura C. Hernández-Ramírez, Sonal Kapur, Francisca Caimari, Jane Evanson, Francesco Ferraù, Mary N. Dang, Plamena Gabrovska, Sarah J. Larkin, Olaf Ansorge, Celia Rodd, Mary L. Vance, Claudia Ramírez-Renteria, Moisés Mercado, Anthony P. Goldstone, Michael Buchfelder, Christine P. Burren, Alper Gurlek, Pinaki Dutta, Catherine S. Choong, Timothy Cheetham, Giampaolo Trivellin, Constantine A. Stratakis, Maria-Beatriz Lopes, Ashley B. Grossman, Jacqueline Trouillas, James R. Lupski, Sian Ellard, Julian R. Sampson, Federico Roncaroli, Márta Korbonits

Abstract

Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly.We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants.We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes in found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic of familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases.In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 92 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 92 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 14 15%
Student > Ph. D. Student 12 13%
Other 10 11%
Student > Bachelor 8 9%
Student > Master 8 9%
Other 17 18%
Unknown 23 25%
Readers by discipline Count As %
Medicine and Dentistry 30 33%
Biochemistry, Genetics and Molecular Biology 14 15%
Agricultural and Biological Sciences 4 4%
Pharmacology, Toxicology and Pharmaceutical Science 3 3%
Nursing and Health Professions 2 2%
Other 15 16%
Unknown 24 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 June 2016.
All research outputs
#15,694,282
of 23,321,213 outputs
Outputs from Acta Neuropathologica Communications
#1,166
of 1,414 outputs
Outputs of similar age
#213,545
of 340,618 outputs
Outputs of similar age from Acta Neuropathologica Communications
#30
of 34 outputs
Altmetric has tracked 23,321,213 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,414 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.8. This one is in the 12th percentile – i.e., 12% of its peers scored the same or lower than it.
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