Nora Sanguineti1, Debora Braslavsky1, Paula A Scaglia1, Ana Keselman1, Maria G Ballerini1, Maria G Ropelato1, Sofia Suco1, Sebastian Vishnopolska2, Ariel J Berenstein3, Héctor Jasper1, Horacio M Domené1, Rodolfo A Rey1, Maria I Pérez Millán4, Sally A Camper5, Ignacio Bergadá6. 1. Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. 2. Department of Biological Chemistry (IQUIBICEN-UBA-CONICET), Faculty of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina. 3. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP), CONICET-GCBA, Laboratorio de Biología Molecular, División Patología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. 4. Institute of Biomedical Investigations (INBIOMED-UBA-CONICET), University of Buenos Aires, Buenos Aires, Argentina. 5. Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA. 6. Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. Electronic address: ibergada@cedie.org.ar.
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).
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).
Authors: Eduardo Adrian Chaler; G abriela Ballerini; Juan M Lazzati; Mercedes Maceiras; Mauro Frusti; Ignacio Bergada; Marco A Rivarola; Alicia Belgorosky; Gabriela Ropelato Journal: Clin Chem Lab Med Date: 2013-05 Impact factor: 3.694
Authors: Rizwan Hamid; John A Phillips; Cindy Holladay; Joy D Cogan; Eric D Austin; Philippe F Backeljauw; Sharon H Travers; James G Patton Journal: J Clin Endocrinol Metab Date: 2009-10-16 Impact factor: 5.958
Authors: María I Pérez Millán; Sebastian A Vishnopolska; Alexandre Z Daly; Juan P Bustamante; Adriana Seilicovich; Ignacio Bergadá; Débora Braslavsky; Ana C Keselman; Rosemary M Lemons; Amanda H Mortensen; Marcelo A Marti; Sally A Camper; Jacob O Kitzman Journal: Mol Genet Genomic Med Date: 2018-05-08 Impact factor: 2.183