Broadening the Phenotype of Human STAT5b Mutations

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Vidarsdottir and colleagues from Leiden, The Netherlands reported an extremely interesting adult patient with molecular evidence of a homozygous mutation in the STAT5b gene. This patient presented certain new features not included in the 2 previous publications of this human gene defect.^1,2 Firstly, this patient was a male, whereas the other cases reported were females, as are 2 further cases in a manuscript in preparation.³ The patient had a normal birth weight, and his parents were non-consanguineous and of normal height. He had congenital ichthyosis and developed hemorrhagic varicella at the age of 16 years, but recovered fully. He had delayed puberty which eventually progressed to maturity. As an adult, he was abnormally short (–5.9 SD), with rather small testes (12 mL).

Biochemically, at the age of 30 years, he had extremely low levels of insulin-like growth factor (IGF)-I, IGF binding-protein (IGFBP)-3, and acid-labile subunit (ALS), associated with normal–but not excessive–growth hormone (GH) secretion. His serum prolactin was elevated. A trial of GH therapy was ineffective. There was no evidence of immunological deficit. Analysis of the STAT5b gene demonstrated a homozygous frameshift mutation resulting in an inactive truncated protein lacking most of the DNA-binding domain and the SH2-domain. No STAT5b protein could be detected in the patient’s fibroblasts.

Vidarsdottir S, Walenkamp MJ, Pereira AM, et al. Clinical and biochemical characteristics of a male patient with a novel homozygous STAT5b mutation. J Clin Endocrinol Metab. 2006;91:3482-5.

Editor’s Comment

The interesting and new features of this patient are: his gender, the apparent lack of immune deficiency, the normal GH secretion despite extreme deficiency of IGF-I, and the hyperprolactinaemia. As in many human single gene defects (eg, GH receptor and IGF-I gene mutations), heterogeneity of the clinical and biochemical phenotypes emerge when the number of cases described increases. This case is particularly interesting because of the absence of immune deficiency compared with the severe and possibly life-threatening immunological complications of 4 known female patients with defects in the same gene.

Martin O. Savage, MD

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Last Updated: 04/30/2008