p.R209H GH1 variant challenges short stature assessment

SANGUINETI, NORA; BRASLAVSKY, DEBORA; SCAGLIA, PAULA A.; KESELMAN, ANA; BALLERINI, MARIA G.; ROPELATO, MARIA G.; SUCO, SOFIA; VISHNOPOLSKA, SEBASTIAN; BERENSTEIN, ARIEL J.; JASPER, HÉCTOR; DOMENÉ, HORACIO M.; REY, RODOLFO A.; PÉREZ MILLÁN, MARIA I.; CAMPER, SALLY A.; BERGADÁ, IGNACIO

GROWTH HORMONE & IGF RESEARCH : OFFICIAL JOURNAL OF THE GROWTH HORMONE RESEARCH SOCIETY AND THE INTERNATIONAL IGF RESEARCH SOCIETY.

CHURCHILL LIVINGSTONE

Año: 2020 vol. 50 p. 23 - 26

1096-6374

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).