STAT5B deficiency: Impacts on human growth and immunity.

Area of Science:

• Endocrinology
• Immunology
• Genetics

Background:

• Growth hormone (GH) drives postnatal growth via the GH receptor (GHR)-STAT5B pathway, regulating insulin-like growth factor (IGF)-I.
• STAT5B is essential for IGF-I production, as demonstrated by a patient with STAT5B deficiency presenting with growth hormone insensitivity (GHI) phenotypes.

Purpose of the Study:

• To highlight the critical role of STAT5B in human growth and IGF-I production.
• To underscore the potential for STAT5B deficiency to cause primary immunodeficiency and chronic pulmonary disease.

Main Methods:

• Case identification of homozygous, autosomal recessive STAT5B mutations.
• Phenotypic analysis of patients with STAT5B deficiency.
• Comparison with GHR mutations and classical GHI syndrome.

Main Results:

• The first homozygous STAT5B mutation identified in a patient with severe postnatal growth failure and IGF-I deficiency.
• STAT5A could not compensate for the loss of STAT5B function.
• STAT5B deficiency is associated with primary immunodeficiency and chronic pulmonary disease, distinct from GHR deficiency.
• Seven homozygous, inactivating STAT5B mutations reported in 10 patients.

Conclusions:

• STAT5B is indispensable for postnatal growth and IGF-I regulation.
• STAT5B deficiency presents a unique syndrome including growth failure and primary immunodeficiency.
• STAT5B deficiency may be underdiagnosed in endocrine, immunology, and pulmonary settings.