CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
artículos
Título:
Genetic Analysis of Short Children with Apparent Growth Hormone Insensitivity
Autor/es:
JAN MAARTEN WIT; H.A. VAN DUYVENVOORDE; S.A. SCHELTINGA; S. DE BRUIN; L. HAFKENSCHEID; S.G. KANT ; C.A.L. RUIVENKAMP; A.C.J. GIJSBERS; J. VAN DOORN; E. FEIGERLOVA; C. NOORDAM; M.J. WALENKAMP; H. CLAAHSEN-VAN DE GRINTEN; P. STOUTHART; I.E. BONAPART; A.M. PEREIRA; J. GOSEN; H.M. DOMENÉ; W. OOSTDIJK; M. LOSEKOOT
Revista:
HORMONE RESEARCH
Editorial:
KARGER
Referencias:
Lugar: Basel; Año: 2012 vol. 77 p. 320 - 333
ISSN:
0301-0163
Resumen:
Abstract 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.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.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.