CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Recurrent R183H GH1 Gene Mutation in a Patient with Autosomal Dominant Isolated Growth Hormone Deficiency (IGHD)
Autor/es:
MARTÍNEZ, ALICIA; SCAGLIA, PAULA; ROPELATO, GABRIELA; HEINRICH, JUAN JORGE; JASPER, HÉCTOR; DOMENÉ, HORACIO
Lugar:
Montevideo
Reunión:
Congreso; XXIII Reunión anual de la Sociedad Latinoamericana Endocrinologia Pediatrica; 2012
Institución organizadora:
Sociedad Latinoamericana Endocrinologia Pediatrica
Resumen:
Introduction: IGHD type II results from autosomal dominant(AD) GH1 gene molecular defects. Aim: To characterizethe molecular alteration of a short male child. Subject andMethods: The patient, a boy born from non consanguineous parents,presented at chronological age (CA) 5.13 years: height 3.36SDS, prominent forehead, mild facial hypoplasia and normal neuro logical development. MRI showed pituitary hypoplasia. His father (height 142.5 cm, 4.46 SDS) presented typical features of IGHD, while his mother (height 152.6 cm, 1.33 SDS) was not clinically affected. GH secretion was assessed by ICMA after sequential arginine-clonidine test and IGF-I by RIA. The whole GH1 gene was PCR amplified and automatically sequenced. Results: IGHD was confirmed by low stimulated GH (GHmax: 2.2 ng/ml), undetectable IGF-I levels, normal TSH response to TRH and normal PRL and cortisol levels. The patient received rhGH replacementtherapy for 9.3 years with good growth response. He began puberty at 12 CA and at 15 years of age had a height of 0.88 SDS, G5,PH5, T15/15. GH1 gene sequencing revealed a c.626G>A transitionin exon 5, predicted to result in the missense mutation p.R183H. Conclusions: The finding of the recurrent R183H mutation, characterized in more than 40 subjects worldwide and presenting a large phenotypic variability, ranging from normal stature and GH secretion to complete GHD, could be responsible for the AD type II IGHD in this patient.