2006, Número 5
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Bol Med Hosp Infant Mex 2006; 63 (5)
Bases moleculares del hipotiroidismo congénito
Pinzón-Serrano E, Morán-Barroso V, Coyote-Estrada N
Idioma: Español
Referencias bibliográficas: 27
Paginas: 351-359
Archivo PDF: 85.21 Kb.
RESUMEN
Las alteraciones endocrinológicas constituyen parte importante de la consulta pediátrica, la más frecuente es el hipotiroidismo congénito, grave problema de salud pública que requiere de diagnóstico neonatal. Los avances en el estudio molecular han permitido discernir las alteraciones en los procesos de organogénesis y hormonogénesis que lo producen. Se describen las principales alteraciones moleculares relacionadas con: diferenciación tiroidea, síntesis hormonal, hipotiroidismo central y con su acción periférica. El estudio de las alteraciones moleculares abre posibilidades interesantes, pues a partir del conocimiento preciso de los procesos fisiopatológicos y moleculares podrá realizarse en forma precoz el diagnóstico y manejo de estos pacientes, previniendo las secuelas que genera esta enfermedad.
REFERENCIAS (EN ESTE ARTÍCULO)
Burrow GN, Fisher DA, Larsen PR. Mechanisms of disease: Maternal and fetal thyroid function. N Engl J Med. 1994; 331: 1072-8.
Thorpe-Beeston JG, Nicolaides KH, Felton CV. Maturation of the secretion of thyroid hormone and thyroid-stimulating hormone in the fetus. N Engl J Med. 1991; 324: 532-6.
Roberts C, Laderson P. Hypothyroidism. Lancet. 2004; 363: 793-803.
Dorantes L. Biosíntesis de las Hormonas Tiroideas en: Programa de Actualización Continua en Pediatría, Academia Mexicana de Pediatría. México: Intersistemas SA de CV; 2005. p. 191-3.
Reed-Larsen P, Davies T, Schlumberger M. Fisiología. Yodo, síntesis y secreción de las hormonas tiroideas. En: Williams, editor. Tratado de endocrinologia. España: Elsevier; 2003. p. 366-7.
Ching-Wan L, On-Kei C, Sui-Fan T, Chi-Chung S, Sau-Cheung T. DNA-based diagnosis of thyroid hormone resistance syndrome: A novel THRB mutation associated with mild resistance to thyroid hormone. Clin Chim Acta. 2005; 358: 55–9.
Park SM, Chatterje VK. Genetics of congenital hypothyroidism. J Med Genet. 2005; 42: 379-89.
Moreno JC, Vijlder JJM, Vulsma T, Ris-Stalpers C. Genetic basis of hypothyroidism: recent advances, gaps and strategies for future research. Trends Endocrinol Metab. 2003; 14: 318-26.
Clifton-Bligh RJ. Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia. Nat Genet. 1998; 19: 399-401.
Castanet M, Park S, Smith A, Bost M. A novel lost-of-function in TTF.2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate. Hum Mol Genet. 2002; 11: 2051-9.
Lonigro R, Donnini D, Zappia E, Damante G, Bianchi M, Guazzi S. Nestin is a neuroepithelial target gene of thyroid transcription factor-1, a homeoprotein required for forebrain organogenesis. J Biol Chem. 2001; 276: 47807-13.
Iwatani N, Mabe H, Devrient K, Kodama M, Müke T. Deletion of NKX2.1 gene encoding thyroid transcription factor -1 in two siblings with hypothyroidism and respiratory failure. J Pediatr. 2000; 137: 272-6.
Doyle D, Gonzalez I, Thomas B, Scavina M. Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of Nkx2-1. J Pediatr. 2004; 145: 190-3.
Rohr K, Concha M. Expression of nk2.1a during early development of the thyroid gland in zebrafish. Mech Dev. 2000: 267-70.
Tanaka M, Wechsler SB, Lee IW, Yamasaki N, Lawitts JA, Izumo S. Complex modular cis-acting elements regulate expression of the cardiac specifying homeobox gene Csx/Nkx2.5. Development. 1999; 126: 1439-50.
Reamon-Buettner S, Hecker H, Spanel-Borowski K, Craatz s, Kuenzel E, Borlak J. Novel NKX2-5 mutations in diseased heart tissues of patients with cardiac malformations. Am J Pathol. 2004; 164: 2117-25.
Dentice M, Morisco C, Vitale M, Rossi G, Fenzi G, Salvatore D. The different cardiac expression of the type 2 iodothyronine deiodinase gene between human and rat is related to the differential response of the dio2 genes to Nkx-2.5 and GATA-4 transcription factors. Mol Endocrinol. 2003; 17: 1508-21.
Dentice M, Cordeddu V, Rosica A, Ferrara AM, Santarpia L, Salvatore D, et al. Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis. J Clin Endocrinol Metab. 2006; 91: 1428-33.
De Felice M, Di Lauro R. Thyroid development and its disorders: Genetics and molecular mechanisms. Endocr Rev. 2004; 25: 722-46.
Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R, et al. Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. Nat Genet. 2001; 28: 375-80.
Vilain C, Rydlewski C, Dupez L, Heinrichs C, Abramowicz, Malvaux P, et al. Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8. J Clin Endocrinol Metab. 2001; 86: 234–8.
Meeus L, Gilbert B, Rydlewski C, Parma J, Roussie AL, Abramowicz M, et al. Characterization of a novel loss of function mutation of PAX8 in a familial case of congenital hypothyroidism with in-place, normal-sized thyroid. J Clin Endocrinol Metab. 2004; 89: 4285-91.
Duprez L, Parma J, van Sande J, Rodien P, Sabine C, Abramowicz M, et al. Pathology of the TSH receptor. J Pediatr Endocrinol Metab. 1999; 12 Supl 1: 295-302.
Moreno J. Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. N Engl J Med. 2002; 347: 95-102.
Yen P. Molecular basis of resistance to thyroid hormones. Trends Endocrinol Metab. 2003; 14: 327-33.
Lamerson JL. Molecular mechanism in end-organ resistance. Growth Hormon IGF Res. 2004; 14: S45-S50.
Zoeller RT. Environmental chemicals as thyroid hormone analogues: New studies indicate that thyroid hormone receptors are targets of industrial chemicals? Mol Cell Endocrinol. 2005; 242: 10-5.