Dataset Information

P.R209H GH1 variant challenges short stature assessment.

ABSTRACT:

Objective

to describe the marked variability in clinical and biochemical patterns that are associated with a p.R209H GH1 missense variant in a large Argentinean pedigree, which makes the diagnosis of GHD elusive.

Design

We describe a non-consanguineous pedigree composed by several individuals with short stature, including 2 pediatric patients with typical diagnosis of isolated growth hormone deficiency (IGHD) and 4 other siblings with severe short stature, low serum IGF-1 and IGFBP-3, but normal stimulated GH levels, suggesting growth hormone insensitivity (GHI) in the latter group.

Results

Patients with classical IGHD phenotype carried a heterozygous variant in GH1: c.626G>A (p.R209H). Data from the extended pedigree suggested GH1 as the initial candidate gene, which showed the same pathogenic heterozygous GH1 variant in the four siblings with short stature and a biochemical pattern of GHI.

Conclusions

We suggest considering GH1 sequencing in children with short stature associated to low IGF-1 and IGFBP-3 serum levels, even in the context of normal response to growth hormone provocative testing (GHPT).

SUBMITTER: Sanguineti N

PROVIDER: S-EPMC7054144 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

p.R209H GH1 variant challenges short stature assessment.

Sanguineti Nora N Braslavsky Debora D Scaglia Paula A PA Keselman Ana A Ballerini Maria G MG Ropelato Maria G MG Suco Sofia S Vishnopolska Sebastian S Berenstein Ariel J AJ Jasper Héctor H Domené Horacio M HM Rey Rodolfo A RA Pérez Millán Maria I MI Camper Sally A SA Bergadá Ignacio I

Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 20191203

<h4>Objective</h4>to describe the marked variability in clinical and biochemical patterns that are associated with a p.R209H GH1 missense variant in a large Argentinean pedigree, which makes the diagnosis of GHD elusive.<h4>Design</h4>We describe a non-consanguineous pedigree composed by several individuals with short stature, including 2 pediatric patients with typical diagnosis of isolated growth hormone deficiency (IGHD) and 4 other siblings with severe short stature, low serum IGF-1 and IGFB ...[more]

PMID: 31835104

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