A Novel Exonic GHR Splicing Mutation (c.784G>C) in a Patient with Classical Growth Hormone Insensitivity Syndrome

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dc.authoridAkinci, Aysehan/0000-0001-7267-9444
dc.authorwosidAkinci, Aysehan/AAC-6847-2021
dc.contributor.authorAkinci, Aysehan
dc.contributor.authorRosenfeld, Ron G.
dc.contributor.authorHwa, Vivian
dc.date.accessioned2024-08-04T20:37:25Z
dc.date.available2024-08-04T20:37:25Z
dc.date.issued2013
dc.departmentİnönü Üniversitesien_US
dc.description.abstractContext: Undetectable circulating growth hormone-binding protein (GHBP) can be indicative of a GH receptor (GHR) defect and cause GH insensitivity (GHI) syndrome. Case Report: The proband, severely growth retarded from birth, had a height of 73 cm (-6 SDS) and weight of 10.5 kg (-2.5 SDS) at the age of 3.25 years; her consanguineous parents were normal statured. Basal serum GH measurement was high, >40 ng/ml, while serum insulin-like growth factor-I (IGF-I; 8.5 ng/ml; normal, 13-100), IGF-binding protein 3 (126 ng/ml; normal, 365-1,294), acid labile subunit (0.59 mg/l; normal, 5.6-16), and GHBP (120 pmol/l; normal, 431-1,892) concentrations were all markedly low. Recombinant IGF-I therapy improved height to -4.4 SDS after 2.5 years of treatment. Results: GHR gene analysis revealed a homozygous c.784G>C transversion, the last nucleotide of exon 7; the parents were heterozygous for the mutation. Evaluation of GHR mRNA indicated c.784G>C was not a missense mutation but induced exon 7 excision, leading to a frame shift and predicted early protein termination. Conclusion: A novel homozygous GHR c.784G>C mutation, identified in a GHI patient, induced functional loss of the native intron 7 donor splice site, demonstrating, for the first time, the importance of exonic nucleotides at exon-intron junctions for normal GHR splicing. Copyright (C) 2012 S. Karger AG, Baselen_US
dc.description.sponsorshipTercica Inc.en_US
dc.description.sponsorshipThis work was funded by a grant from Tercica Inc. (to R.G.R.). R.G.R. has received payments for consulting or lectures from Tercica. This potential conflict of interest has been reviewed and managed by OHSU.en_US
dc.identifier.doi10.1159/000341527
dc.identifier.endpage38en_US
dc.identifier.issn1663-2818
dc.identifier.issue1en_US
dc.identifier.pmid23006617en_US
dc.identifier.scopus2-s2.0-84873705414en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage32en_US
dc.identifier.urihttps://doi.org/10.1159/000341527
dc.identifier.urihttps://hdl.handle.net/11616/95950
dc.identifier.volume79en_US
dc.identifier.wosWOS:000318476200007en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherKargeren_US
dc.relation.ispartofHormone Research in Paediatricsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectGrowth hormone insensitivityen_US
dc.subjectc.784G > C mutationen_US
dc.subjectExon-intron junctionsen_US
dc.subjectGHR splicingen_US
dc.subjectInsulin-like growth factor-I therapyen_US
dc.titleA Novel Exonic GHR Splicing Mutation (c.784G>C) in a Patient with Classical Growth Hormone Insensitivity Syndromeen_US
dc.typeArticleen_US

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