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@article{Iacovazzo:2016:10.1186/s40478-016-0328-1,
author = {Iacovazzo, D and Caswell, R and Bunce, B and Jose, S and Yuan, B and Hernández-Ramírez, LC and Kapur, S and Caimari, F and Evanson, J and Ferraù, F and Dang, MN and Gabrovska, P and Larkin, SJ and Ansorge, O and Rodd, C and Vance, ML and Ramírez-Renteria, C and Mercado, M and Goldstone, AP and Buchfelder, M and Burren, CP and Gurlek, A and Dutta, P and Choong, CS and Cheetham, T and Trivellin, G and Stratakis, CA and Lopes, MB and Grossman, AB and Trouillas, J and Lupski, JR and Ellard, S and Sampson, JR and Roncaroli, F and Korbonits, M},
doi = {10.1186/s40478-016-0328-1},
journal = {Acta Neuropathologica Communications},
title = {Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study},
url = {http://dx.doi.org/10.1186/s40478-016-0328-1},
volume = {4},
year = {2016}
}

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TY  - JOUR
AB  - 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 duplicati
AU  - Iacovazzo,D
AU  - Caswell,R
AU  - Bunce,B
AU  - Jose,S
AU  - Yuan,B
AU  - Hernández-Ramírez,LC
AU  - Kapur,S
AU  - Caimari,F
AU  - Evanson,J
AU  - Ferraù,F
AU  - Dang,MN
AU  - Gabrovska,P
AU  - Larkin,SJ
AU  - Ansorge,O
AU  - Rodd,C
AU  - Vance,ML
AU  - Ramírez-Renteria,C
AU  - Mercado,M
AU  - Goldstone,AP
AU  - Buchfelder,M
AU  - Burren,CP
AU  - Gurlek,A
AU  - Dutta,P
AU  - Choong,CS
AU  - Cheetham,T
AU  - Trivellin,G
AU  - Stratakis,CA
AU  - Lopes,MB
AU  - Grossman,AB
AU  - Trouillas,J
AU  - Lupski,JR
AU  - Ellard,S
AU  - Sampson,JR
AU  - Roncaroli,F
AU  - Korbonits,M
DO  - 10.1186/s40478-016-0328-1
PY  - 2016///
SN  - 2051-5960
TI  - Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study
T2  - Acta Neuropathologica Communications
UR  - http://dx.doi.org/10.1186/s40478-016-0328-1
UR  - http://hdl.handle.net/10044/1/33573
VL  - 4
ER  -

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