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http://purl.uniprot.org/citations/14678285http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14678285http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14678285http://www.w3.org/2000/01/rdf-schema#comment"

Objective

The study describes for the first time, a homozygous mutation in the WSXWS-like motif of the human GH receptor (GHR) in a patient with Laron syndrome and describe laboratory data during treatment with GnRHa to suppress puberty and dihydrotestosterone (DHT).

Patients

A 16-year-old boy at Tanner puberty stage 2 with Laron syndrome was born SGA to consanguineous parents, presented severe growth retardation, obesity and micropenis.

Methods and measurements

GHR coding region was sequenced. GH, GHBP, IGF-I and IGFBP-3 were determined before, during and after GnRHa and DHT treatment.

Results

A homozygous mutation in exon 7, replacing serine by isoleucine in codon 226 was identified. S226 is the last serine belonging to the WSXWS-like motif in GHR. No specific effect of S226I mutation in heterozygous state was observed. Laboratory data at the prepubertal age showed markedly high GH, low GHBP, IGF-I and IGFBP-3 levels. Re-evaluation at pubertal age showed normal basal serum IGFBP-3 levels and low but near normal IGF-I levels. We also noticed a sustained decrease in GH, IGF-I and IGFBP-3 levels after blocking puberty, which was not affected by short- and long-term DHT treatment. Pubertal hormonal profile was re-established after the GnRHa therapy was discontinued to allow the reactivation of the gonadal axis.

Conclusion

The homozygous mutation S226I in WSXWS-like motif of GHR causes GH insensitivity. The decrease in IGF-I and IGFBP-3 levels after GnRHa therapy, which was not reversed with DHT administration, suggests that sex steroids have, through oestradiol, a GH-independent action on IGF-I and IGFBP-3 levels. A direct effect of GnRHa on GH secretion cannot be excluded."xsd:string
http://purl.uniprot.org/citations/14678285http://purl.org/dc/terms/identifier"doi:10.1111/j.1365-2265.2004.01930.x"xsd:string
http://purl.uniprot.org/citations/14678285http://purl.org/dc/terms/identifier"doi:10.1111/j.1365-2265.2004.01930.x"xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/author"Mendonca B.B."xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/author"Mendonca B.B."xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/author"Arnhold I.J.P."xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/author"Arnhold I.J.P."xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/author"Jorge A.A.L."xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/author"Jorge A.A.L."xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/author"Souza S.C.A.L."xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/author"Souza S.C.A.L."xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/name"Clin. Endocrinol. (Oxf.)"xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/name"Clin. Endocrinol. (Oxf.)"xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/pages"36-40"xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/pages"36-40"xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/title"The first homozygous mutation (S226I) in the highly-conserved WSXWS-like motif of the GH receptor causing Laron syndrome: suppression of GH secretion by GnRH analogue therapy not restored by dihydrotestosterone administration."xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/title"The first homozygous mutation (S226I) in the highly-conserved WSXWS-like motif of the GH receptor causing Laron syndrome: suppression of GH secretion by GnRH analogue therapy not restored by dihydrotestosterone administration."xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/volume"60"xsd:string
http://purl.uniprot.org/citations/14678285http://purl.uniprot.org/core/volume"60"xsd:string
http://purl.uniprot.org/citations/14678285http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/14678285
http://purl.uniprot.org/citations/14678285http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/14678285
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