Genetic analysis of short children with apparent growth hormone insensitivity

• Autores: Wit, J. M.; Van Duyvenvoorde, H. A.; Scheltinga, S. A.; De Bruin, S.; Hafkenscheid, L.; Kant, S. G.; Ruivenkamp, C. A. L.; Gijsbers, A. C. J.; Van Doorn, J.; Feigerlova, E.; Noordam, C.; Walenkamp, M. J.; Claahsen-Van De Grinten, H.; Stouthart, P.; Bonapart, I. E.; Pereira, A. M.; Gosen, J.; Delemarre-Van De Waal, H.A.; Hwa, V.; Breuning, M.H.; Domene, Horacio Mario; Oostdijk, W.; Losekoot, M.
• Año de publicación: 2012
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Acid-Labile Subunit; Genetics; Gh/Igf-1 Axis; Gh1 Gene; Growth Disorders; Growth Hormone; Growth Hormone Receptor; Igf-1; Stat5b
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Background/Aims: In short children, a low IGF-I and normal GH secretion may be associated with various monogenic causes, but their prevalence is unknown. We aimed at testing GH1, GHR, STAT5B, IGF1, and IGFALS in children with GH insensitivity. Subjects and Methods: Patients were divided into three groups: group 1 (height SDS <-2.5, IGF-I <-2 SDS, n = 9), group 2 (height SDS -2.5 to -1.9, IGF-I <-2 SDS, n = 6) and group 3 (height SDS <-1.9, IGF-I -2 to 0 SDS, n = 21). An IGF-I generation test was performed in 11 patients. Genomic DNA was used for direct sequencing, multiplex ligation-dependent probe amplification and whole-genome SNP array analysis. Results: Three patients in group 1 had two novel heterozygous STAT5B mutations, in two combined with novel IGFALS variants. In groups 2 and 3 the association between genetic variants and short stature was uncertain. The IGF-I generation test was not predictive for the growth response to GH treatment. Conclusion: In severely short children with IGF-I deficiency, genetic assessment is advised. Heterozygous STAT5B mutations, with or without heterozygous IGFALS defects, may be associated with GH insensitivity. In children with less severe short stature or IGF-I deficiency, functional variants are rare. Copyright © 2012 S. Karger AG, Basel.
Fil: Wit, J. M.. Leiden University; Países Bajos
Fil: Van Duyvenvoorde, H. A.. Leiden University; Países Bajos
Fil: Scheltinga, S. A.. Leiden University; Países Bajos
Fil: De Bruin, S.. Leiden University; Países Bajos
Fil: Hafkenscheid, L.. Leiden University; Países Bajos
Fil: Kant, S. G.. Leiden University; Países Bajos
Fil: Ruivenkamp, C. A. L.. Leiden University; Países Bajos
Fil: Gijsbers, A. C. J.. Leiden University; Países Bajos
Fil: Van Doorn, J.. University Medical Center Utrecht; Países Bajos
Fil: Feigerlova, E.. Oregon Health And Science University; Estados Unidos
Fil: Noordam, C.. Radboud University Nijmegen Medical Centre; Países Bajos
Fil: Walenkamp, M. J.. Vrije Universiteit; Países Bajos
Fil: Claahsen-Van De Grinten, H.. Radboud University Nijmegen Medical Centre; Países Bajos
Fil: Stouthart, P.. Orbis Medical Centre; Países Bajos
Fil: Bonapart, I. E.. Venizelion General Hospital; Países Bajos
Fil: Pereira, A. M.. Leiden University; Países Bajos
Fil: Gosen, J.. Rijnland Hospital; Países Bajos
Fil: Delemarre-Van De Waal, H.A.. Leiden University; Países Bajos
Fil: Hwa, V.. Oregon Health And Science University; Estados Unidos
Fil: Breuning, M.H.. Leiden University; Países Bajos
Fil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Fil: Oostdijk, W.. Leiden University; Países Bajos
Fil: Losekoot, M.. Leiden University; Países Bajos