Somatic GPR101 Duplication Causing X-Linked Acrogigantism (XLAG)-Diagnosis and Management.
J Clin Endocrinol Metab
; 101(5): 1927-30, 2016 05.
Article
en En
| MEDLINE
| ID: mdl-26982009
ABSTRACT
CONTEXT Recent reports have proposed that sporadic or familial germline Xq26.3 microduplications involving the GPR101 gene are associated with early-onset X-linked acrogigantism (XLAG) with a female preponderance. CASE DESCRIPTION A 4-year-old boy presented with rapid growth over the previous 2 years. He complained of sporadic headaches and had coarse facial features. His height Z-score was +4.89, and weight Z-score was +5.57. Laboratory testing revealed elevated serum prolactin (185 µg/L; normal, <18 µg/L), IGF-1 (745 µg/L; normal, 64-369 µg/L), and fasting GH > 35.0 µg/L. Magnetic resonance imaging demonstrated a homogenous bulky pituitary gland (18 × 15 × 13 mm) without obvious adenoma. A pituitary biopsy showed hyperplastic pituitary tissue with enlarged cords of GH and prolactin cells. Germline PRKAR1A, MEN1, AIP, DICER1, CDKN1B, and somatic GNAS mutations were negative. Medical management was challenging until institution of continuous sc infusion of short-acting octreotide combined with sc pegvisomant and oral cabergoline. The patient remains well controlled with minimal side effects 7 years after presentation. His phenotype suggested XLAG, but his peripheral leukocyte-, saliva-, and buccal cell-derived DNA tested negative for microduplication in Xq26.3 or GPR101. However, DNA isolated from the pituitary tissue and forearm skin showed duplicated dosage of GPR101, suggesting that he is mosaic for this genetic abnormality. CONCLUSIONS:
Our patient is the first to be described with somatic microduplication leading to typical XLAG phenotype. This patient demonstrates that a negative test for Xq26.3 microduplication or GPR101 duplication on peripheral blood DNA does not exclude the diagnosis of XLAG because it can result from a mosaic mutation affecting the pituitary.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hipófisis
/
Duplicación de Gen
/
Receptores Acoplados a Proteínas G
/
Gigantismo
Tipo de estudio:
Diagnostic_studies
Límite:
Child, preschool
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Humans
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Male
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2016
Tipo del documento:
Article