Pharmacologic correction of dominant-negative GH1 deficiency causing mutations.

Poling JS, Phillips JA, Cogan JD, Hamid R
Clin Transl Sci. 2011 4 (3): 175-9

PMID: 21707947 · PMCID: PMC5439858 · DOI:10.1111/j.1752-8062.2011.00290.x

PURPOSE - Dominant-negative growth hormone gene (GH1) mutations cause familial isolated growth hormone deficiency type II (IGHD II), which is characterized by GH deficiency, occasional multiple anterior pituitary hormone deficiencies, and anterior pituitary hypoplasia. We have previously shown that 17.5-/22-kDa GH1 transcript ratios correlate with the severity of the IGHD II phenotype. We hypothesized that different pharmaceutical agents could affect the GH1 transcript ratio by modulating alternative splicing.

METHODS - We exposed peripheral blood mononuclear cells from IGHD II patients and unaffected family members to different pharmacologic agents and then determined the 17.5-/22-kDa transcript ratios by real-time PCR.

RESULTS - Dexamethasone and digoxin significantly increased the 17.5-/22-kDa transcript ratio, while sodium butyrate and 5-iodotubericidin significantly decreased the ratio.

CONCLUSION - Since we have previously shown that the ratio of the 17.5-/22-kDa GH1 transcripts correlates with severity of the IGHD II phenotype, our findings here suggest that selected previously unconsidered agents could possibly reduce the severity of IGHD II, while other agents could possibly exacerbate the disease phenotype.

© 2011 Wiley Periodicals, Inc.

MeSH Terms (15)

Cell Line Dexamethasone Digoxin Family Health Genes, Dominant Growth Hormone Humans Leukocytes, Mononuclear Mutation Phenotype Pituitary Diseases Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Sodium Oxybate Tubercidin

Connections (1)

This publication is referenced by other Labnodes entities:

Links