Here we report dominant-negative, inactivating STAT5B germline mutations in patients with growth failure, eczema, and elevated IgE but without severe immune and pulmonary problems.
The critical importance of STAT5B in human IGF-I production was confirmed with the identification of the first homozygous, autosomal recessive, STAT5B mutation in a young female patient who phenotypically resembled patients with classical growth hormone insensitivity (GHI) syndrome (Laron syndrome) due to mutations in the GHR gene, presenting with severe postnatal growth failure and marked IGF-I deficiency.
One of four STAT proteins (STAT1, -3, -5a and -5b) activated by the GH-GHR system, the critical importance of STAT5b in IGF-I production became evident with the identification of homozygous, autosomal recessive STAT5b mutations in patients who presented with severe postnatal growth failure, growth hormone insensitivity syndrome (GHIS) and marked IGF-I deficiency.
The identification of a second case of severe growth failure associated with STAT5b mutation implicates a unique and critical role for STAT5b in GH stimulation of IGF-I gene expression and statural growth.