Growth hormone insensitivity and severe short stature in siblings: a novel mutation at the exon 13-intron 13 junction of the STAT5b gene.
OBJECTIVE
Growth hormone insensitivity (GHI) is characterized by severe short stature, high serum growth hormone (GH), low serum IGF-I and IGFBP-3 levels and is classically associated with genetic defects of the GH receptor (GHR). Recently, mutations of the STAT5b gene have been identified and shown to be associated with GHI and severe IGF deficiency. We investigated 2 sisters from a consanguineous family from Kuwait, with clinical and biochemical features of GHI, in whom no molecular defects in the GHR were identified.


METHODS
Serum and DNA were analyzed.


RESULTS
In addition to GHI, siblings 2 and 1 presented with, respectively, a diagnosis of juvenile idiopathic arthritis and recurrent pulmonary infections. Molecular analysis of the STAT5b gene revealed a novel homozygous deletion of a G at the junction of exon 13-intron 13. The parents, who are of normal height, were heterozygous for the mutation.


CONCLUSIONS
This is the first STAT5b defect to be identified in siblings, further supporting the autosomal recessive mode of transmission of STAT5b deficiency. The results affirm that defective STAT5b is an etiology for IGF deficiency and the GHI phenotype, and emphasize the importance of considering this diagnosis in patients with IGF deficiency, especially when associated with diverse immunological problems.
Hwa
Vivian
V
Department of Pediatrics, Oregon Health and Sciences University, Portland, OR 97239-3098, USA.
Camacho-Hübner
Cecilia
C
Little
Brian M
BM
David
Alessia
A
Metherell
Lou A
LA
El-Khatib
Nesrin
N
Savage
Martin O
MO
Rosenfeld
Ron G
RG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001827:Body Height / Q000235:genetics*; D019556:COS Cells; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D046150:Laron Syndrome / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D050799:STAT5 Transcription Factor / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D035781:Siblings; D014162:Transfection
D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human