Study data from University of Buenos Aires update knowledge of congenital hypothyroidism
2007 NOV 20 -- "Thyroid dyshormonogenesis is associated with mutations in the thyroglobulin (TG) gene and characterized by normal organification of iodide and low serum TG. These mutations give rise to congenital goitrous hypothyroidism, transmitted in an autosomal recessive mode," investigators in Buenos Aires, Argentina report. "The aim of this study was to identify new mutations in the TG gene in an attempt to increase the understanding of the molecular basis of this disorder. Three unrelated patients with marked impairment of TG synthesis were studied. The promoter and the complete coding regions of the TG gene, along with the flanking intronic regions, were analysed by direct DNA sequencing. Four different inactivating TG mutations, three novel mutations (c.548G > A, p.C164Y; c.759-760insA, p.L234fsX237; c.6701C > A, p.A2215D) and one previously identified mutation (c.886C > T, p.R277X) were identified. Multiple sequence alignment study revealed that the wild-type cysteine residue at position 164 is strictly conserved in the TG of all the species analysed, whereas the wild-type alanine residue at position 2215 is well conserved in the TG and acetylcholinesterase (AChE) of all the species analysed except in rabbit AChE, in which it is substituted by glutamic acid. We report three patients with congenital hypothyroidism with goitre caused by two compound heterozygous mutations, p.C164Y/p.L234fsX237 and p.R277X/p.A2215D, and one homozygous mutation, p.R277X, in the TG gene," wrote M. Caputo and colleagues, University of Buenos Aires. The researchers concluded: "To our knowledge this is the first report of the presence of a nucleotide insertion mutation in the TG gene." Caputo and colleagues published their study in Clinical Endocrinology (Congenital hypothyroidism with goitre caused by new mutations in the thyroglobulin gene. Clinical Endocrinology, 2007;67(3):351-357). For additional information, contact H.M. Targovnik, University of Buenos Aires, Faculty Farm & Bioquim, Laboratory Biology Molecular, Catedra Genetics & Biology Molecular, Junin 956, RA-1113 Buenos Aires, DF, Argentina. The publisher of the journal Clinical Endocrinology can be contacted at: Blackwell Publishing, 9600 Garsington Rd., Oxford OX4 2DQ, Oxon, England. Keywords: Argentina, Buenos Aires, Congenital Hypothyroidism, Endocrinology, University of Buenos Aires. This article was prepared by Science Letter editors from staff and other reports. Copyright 2007, Science Letter via NewsRx.com.
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