CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
GH insensitivity and immunodeficiency associated with a novel STAT5b gene mutation
Autor/es:
PAULA A, SCAGLIA; ALICIA MARTÍNEZ; MARY RIVAS; LILIANA BEZRODNIK; MARIA GAILLARD; JUAN J HEINRICH; MARIA G. BALLERINI; HÉCTOR G. JASPER; HORACIO M. DOMENÉ
Lugar:
Mar del Plata, Argentina
Reunión:
Congreso; XIX Reunión anual de la Sociedad Latinoamerican de Endocrinología Pediátrica.; 2007
Institución organizadora:
Sociedad Latinoamerican de Endocrinología Pediátrica
Resumen:
GH INSENSITIVITY AND IMMUNODEFICIENCY ASSOCIATED WITH A NOVEL STAT5B GENE MUTATION. 1 CEDIE-CONICET, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina 2 Grupo de Inmunología - Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina 3 División Endocrinología, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina [*] Presenting author Mouse KO models and human STAT5b mutations have demonstrated its requirement for normal IGF-I production and postnatal growth, and also for normal immune function. We describe a female patient, adopted at 4 days of age, with extreme growth retardation associated with severe dermatitis, recurrent respiratory infections, failure to thrive and mildly retarded neurological development. Immunological evaluation showed T lymphopenia, (low CD3, CD4, NK and very low CD8 cell counts), hypergammaglobulinemia, poor proliferative response after antigen stimulation and normal B cell counts. Endocrinological evaluation confirmed GH insensitivity: normal GH response to provocative test, undetectable IGF-I levels, no response of IGF-I or IGFBP-3 to a generation test (11 ng/ml, -4.0 SDS and 1.3 mg/ml, -4.1 SDS respectively), normal GHBP and high PRL levels. She began puberty at 12.5 years of age, reaching menarche at 14.5 years, attaining a near adult height of 124.2 cm (-5.7 SDS). Sequencing of the STAT5b gene exons 8-16, encoding SH2 and DNA binding domains, revealed a homozygous T®C transition in the 2nd base of codon 646, resulting in a missense mutation (p.F646S) which changes a highly conserved hydrophobic residue among STAT proteins. This mutation lies into the SH2 domain, critical for STAT5b recruitment to the activated GHR complex, dimerization, and translocation to the nucleus. These findings support the crucial role of STAT5b in normal IGF-I production and postnatal growth, emphasizing the heterogeneity of the immunodeficiency, with a more consistent severe impact on linear growth.