Pharmacologic correction of dominant-negative GH1 deficiency causing mutations.

ABSTRACT:

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 inc

SUBMITTER: Poling JS 

PROVIDER: S-EPMC5439858 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature