A Novel Missense Mutation in the SH2 Domain of the<i>STAT5B</i>Gene Results in a Transcriptionally Inactive STAT5b Associated with Severe IGF-I Deficiency, Immune Dysfunction, and Lack of Pulmonary Disease

Abstract

A novel STAT5B p.Phe646Ser mutation has been identified in a patient with clinical characteristics of STAT5b deficiency. Only the second STAT5B missense mutation identified, its lack of transcriptional activities despite GH-induced phosphorylation, confirms the crucial role of STAT5b for regulating the expression of IGF1 and provides insights into the importance of the SH2 βD' strand for full STAT5b transcriptional activities. Whether the phosphorylated p.Phe646Ser variant retained functions that prevented pulmonary distress remains unresolved.