Clinical and biochemical characteristics of a male patient with a novel homozygous STAT5b mutation.
BACKGROUND
GH insensitivity can be caused by defects in the GH receptor (GHR) or in the postreceptor signaling pathway. Recently, two female patients with severe growth retardation and pulmonary and immunological problems were described with a defect in STAT5b, a critical intermediary of downstream GHR signaling.


OBJECTIVE
The objective was to determine the functional characteristics of a novel STAT5b mutation and describe the phenotype.


METHODS
We describe an adult male patient with short stature [-5.9 sd score (SDS)], delayed puberty, and no history of pulmonary or immunological problems. GH-binding protein level as well as GH secretion characteristics were normal. Plasma prolactin level was elevated. Extremely low levels of IGF-I (-6.9 SDS), IGF-binding protein-3 (-12 SDS), and acid-labile subunit (-7.5 SDS) were found.


RESULTS
We found a homozygous frameshift mutation in the STAT5b gene (nucleotide 1102-3insC, Q368fsX376), resulting in an inactive truncated protein, lacking most of the DNA binding domain and the SH2-domain.


CONCLUSIONS
This report confirms the essential role of STAT5b in GH signaling in the human. We show for the first time that immunological or pulmonary problems or elevated GH secretion are not obligatory signs of STAT5b deficiency, whereas hyperprolactinemia appears to be part of the syndrome. Therefore, in patients with severe short stature, signs of GH insensitivity, and a normal GHR, analysis of the STAT5b gene is recommended.
Vidarsdottir
Solrun
S
Department of Pediatrics J6-S, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Walenkamp
Marie J E
MJ
Pereira
Alberto M
AM
Karperien
Marcel
M
van Doorn
Jaap
J
van Duyvenvoorde
Hermine A
HA
White
Stefan
S
Breuning
Martijn H
MH
Roelfsema
Ferdinand
F
Kruithof
M Femke
MF
van Dissel
Jaap
J
Janssen
Riny
R
Wit
Jan M
JM
Romijn
Johannes A
JA
D000328:Adult; D001483:Base Sequence; D002352:Carrier Proteins / Q000097:blood; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D006023:Glycoproteins / Q000097:blood; D006130:Growth Disorders / Q000097:blood / Q000235:genetics*; D019382:Human Growth Hormone / Q000502:physiology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D050799:STAT5 Transcription Factor / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction
D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; C075944:insulin-like growth factor binding protein, acid labile subunit; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004247:DNA