AI Article Synopsis
- * The duplication modifies the normal gene arrangement, leading to increased hormone production and causing gigantism due to a new regulatory domain (neo-TAD) that disrupts typical genetic control.
- * The case study of a female patient highlights the challenges in diagnosing and treating X-LAG, showcasing the use of advanced medical techniques and surgical interventions to achieve hormone regulation in affected children.
Article Abstract
X-linked acrogigantism (X-LAG) is a rare form of pituitary gigantism that is associated with growth hormone (GH) and prolactin-secreting pituitary adenomas/pituitary neuroendocrine tumors (PitNETs) that develop in infancy. It is caused by a duplication on chromosome Xq26.3 that leads to the misexpression of the gene , a constitutively active stimulator of pituitary GH and prolactin secretion. normally exists within its own topologically associating domain (TAD) and is insulated from surrounding regulatory elements. X-LAG is a TADopathy in which the duplication disrupts a conserved TAD border, leading to a neo-TAD in which ectopic enhancers drive over-expression, thus causing gigantism. Here we trace the full diagnostic and therapeutic pathway of a female patient with X-LAG from 4C-seq studies demonstrating the neo-TAD through medical and surgical interventions and detailed tumor histopathology. The complex nature of treating young children with X-LAG is illustrated, including the achievement of hormonal control using a combination of neurosurgery and adult doses of first-generation somatostatin analogs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10932951 | PMC |
| http://dx.doi.org/10.3389/fendo.2024.1345363 | DOI Listing |
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