Genomic rearrangements identified in eight subjects with duplications encompassing GPR101. The online version of this article (doi:10.1186/s4047-1) contains supplementary material, which is available to authorized users. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region.
In conclusion, XLAG can result from germline or somatic duplication of GPR101. 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. Sparsely and densely granulated somatotrophs were admixed with lactotrophs follicle-like structures and calcifications were commonly observed. These tumors had a sinusoidal and lobular architecture. The pathological features of XLAG-related adenomas were remarkably similar. 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. Nine patients had pituitary adenomas, while three had hyperplasia. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. 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. We identified 12 patients (10 females and 2 males 7.8 %) with XLAG. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants. The genetic, clinical and histopathological features of XLAG patients were studied in detail. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. We studied 153 patients (58 females and 95 males) with pituitary gigantism. 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.
Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG).
0 kommentar(er)
