Producción CyT
Artículo
Autoría
Keselman, Ana Claudia
;
MARTIN, AYELEN
;
SCAGLIA, PAULA ALEJANDRA
;
Sanguineti, Nora María
;
Armando, Romina
;
Gutiérrez, Mariana Lilián
;
Braslavsky, Debora Giselle
;
Ballerini, Maria Gabriela
;
ROPELATO, MARIA GABRIELA
;
Ramirez, Laura Beatriz
;
Landi, Estefania Maria
;
DOMENE, SABINA
;
Castro, Julia
;
Cassinelli, Hamilton Raul
;
Casali, Bárbara María de Los Angeles M
;
del Rey, Graciela Monica
;
Campos-Barros, Angel
;
Nevado Blanco, Julián
;
Domene, Horacio Mario
;
Jasper, Hector Guillermo
;
Arberas, Claudia Liliana
;
REY, RODOLFO ALBERTO
;
Lapunzina Badía, Pablo
;
BERGADÁ, IGNACIO
;
PENNISI, PATRICIA ALEJANDRA
Fecha
2019
Editorial y Lugar de Edición
BIOSCIENTIFICA LTD
Revista
EUROPEAN JOURNAL OF ENDOCRINOLOGY,
vol. 181
(pp. 1-11)
BIOSCIENTIFICA LTD
Resumen
Información suministrada por el agente en
SIGEVA
Background: IGF1 is a key factor in fetal and postnatal growth. To date, only three homozygous IGF1 gene defectsleading to complete or partial loss of IGF1 activity have been reported in three short patients born small forgestational age. We describe the fourth patient with severe short stature presenting a novel homozygous IGF1 genemutation.Results: We report a boy born from consanguineous parents at 40 weeks of gestational age with intrauterinegrowth restriction and severe postnatal growth fa...
Background: IGF1 is a key factor in fetal and postnatal growth. To date, only three homozygous IGF1 gene defectsleading to complete or partial loss of IGF1 activity have been reported in three short patients born small forgestational age. We describe the fourth patient with severe short stature presenting a novel homozygous IGF1 genemutation.Results: We report a boy born from consanguineous parents at 40 weeks of gestational age with intrauterinegrowth restriction and severe postnatal growth failure. Physical examination revealed proportionate short stature,microcephaly, facial dysmorphism, bilateral sensorineural deafness and mild global developmental delay. Basalgrowth hormone (GH) fluctuated from 0.2 to 29?ng/mL, while IGF1 levels ranged from ?1.15 to 2.95 SDS. IGFBP3 wasnormal-high. SNP array delimited chromosomal regions of homozygosity, including 12q23.2 where IGF1 is located.IGF1 screening by HRM revealed a homozygous missense variant NM_000618.4(IGF1):c.322T>C, p.(Tyr108His). Thechange of the highly conserved Tyr60 in the mature IGF1 peptide was consistently predicted as pathogenic by multiplebioinformatic tools. Tyr60 has been described to be critical for IGF1 interaction with type 1 IGF receptor (IGF1R). Invitro, HEK293T cells showed a marked reduction of IGF1R phosphorylation after stimulation with serum from thepatient as compared to sera from age-matched controls. Mutant IGF1 was also less efficient in inducing cell growth.Conclusion: The present report broadens the spectrum of clinical and biochemical presentation of homozygous IGF1defects and underscores the variability these patients may present depending on the IGF/IGF1R pathway activity.
Ver más
Ver menos
Palabras Clave
IGF-1
Descargue o solicite el texto completo