Isolated GHD: investigation and implication of JAK/STAT related genes before and after rhGH treatment.
Isolated GH deficiency (IGHD) is a rare disorder that occurs as an idiopathic form in most cases. The pathway JAK/STAT promotes cellular growth and it could be implicated in this condition. In order to characterize IGHD in the pediatric population and identify genes differently expressed before and after GH therapy, we performed a quantitative evaluation of 84 genes related to the JAK/STAT pathway which, by promoting cellular growth. RT(2) Profiler PCR Array and the other/subsequent evaluations were performed in three children with severe IGHD before and after 6 months of GH therapy and in three matched normal children. Gene profiling was modified by the IGHD status and the GH therapy, with a modulation of GHR and some inflammatory genes such as CRP. We found a heterozygous nonsense mutation R43X in the GHR gene in two out of three IGHD subjects, despite a good response to therapy. After therapy cardiovascular markers linked to genes as IL6, IL8 and TNF-α displayed a trend toward reduction. Pre- and post therapy status differently affects gene expression. Mutational screening of GHR may be useful in investigating IGHD's etiology. Genes linked to inflammation suggest to evaluate cardiovascular risks also in pediatric IGHD subjects.
Division of Pediatrics, Department of Medical Science, University A Avogadro of Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy. letizia.trovato@med.unipmn.it
Letizia
L
Trovato
Stefania
S
Riccomagno
Flavia
F
Prodam
Giulia
G
Genoni
Gillian E
GE
Walker
Stefania
S
Moia
Simonetta
S
Bellone
Gianni
G
Bona
D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D004393:Dwarfism, Pituitary / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002352:Carrier Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D050791:STAT Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D019382:Human Growth Hormone; D053612:Janus Kinases; C051815:somatotropin-binding protein