A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblings.
BACKGROUND
GH insensitivity (GHI) syndrome caused by STAT5B mutations was recently reported, and it is characterized by extreme short stature and immune dysfunction. Treatment with recombinant human IGF1 (rhIGF1) is approved for patients with GHI, but the growth response to this therapy in patients with STAT5B mutations has not been reported.


OBJECTIVE
To report the clinical features, molecular findings, and the short-term growth response to rhIGF1 therapy in patients with STAT5B mutation.


METHODS
Hormonal and immunological evaluations were performed in two male siblings with GHI associated with atopic eczema, interstitial lung disease, and thrombocytopenic purpura. STAT5B genes were directly sequenced. The younger sibling was treated with rhIGF1 at a dose of 110 microg/kg BID.


RESULTS
Both siblings had laboratory findings compatible with GHI associated with hyperprolactinemia. Lymphopenia and reduced number of natural killer cells without immunoglobulin abnormalities were observed. STAT5B sequence revealed a homozygous frameshift mutation (p.L142fsX161) in both siblings. The younger sibling (9.9 years of age) was treated with rhIGF1 at appropriate dosage, and he did not present any significant change in his growth velocity (from 2.3 to 3.0 cm/year after 1.5 years of therapy). The presence of a chronic illness could possibly be responsible for the poor result of rhIGF1 treatment. Further studies in patients with STAT5B defects are necessary to define the response to rhIGF1 treatment in this disorder.


CONCLUSIONS
GHI associated with immune dysfunction, especially interstitial lung disease, and hyperprolactinemia is strongly suggestive of a mutation in STAT5B in both sexes.
Unidade de Endocrinologia do Desenvolvimento, Hospital das Clinicas, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
Patricia N
PN
Pugliese-Pires
Carlos A
CA
Tonelli
Jose M
JM
Dora
Paulo C A
PC
Silva
Mauro
M
Czepielewski
Genoir
G
Simoni
Ivo J P
IJ
Arnhold
Alexander A L
AA
Jorge
D000328:Adult; D002648:Child; D002675:Child, Preschool; D006130:Growth Disorders / Q000235:genetics* / Q000628:therapy; D006801:Humans; D006966:Hyperprolactinemia / Q000235:genetics*; D007154:Immune System Diseases / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D011994:Recombinant Proteins / Q000627:therapeutic use; D050799:STAT5 Transcription Factor / Q000235:genetics*; D035781:Siblings
D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D007334:Insulin-Like Growth Factor I