Congenital Hypothyroidism
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What is congenital hypothyroidism?Congenital hypothyroidism is a condition that affects infants from birth (congenital) and results from a partial or complete loss of thyroid function (hypothyroidism). The thyroid gland is a butterfly-shaped tissue in the lower neck. It makes iodine-containing hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). Congenital hypothyroidism occurs when the thyroid gland fails to develop or function properly. In 80 to 85 percent of cases, the thyroid gland is absent, abnormally located, or severely reduced in size (hypoplastic). In the remaining cases, a normal-sized or enlarged thyroid gland is present, but production of thyroid hormones is decreased or absent. If untreated, congenital hypothyroidism can lead to mental retardation and abnormal growth. In the United States and many other countries, all newborns are tested for congenital hypothyroidism. If treatment begins in the first month after birth, infants usually develop normally. How common is congenital hypothyroidism?Studies of populations from North America, Europe, Japan, and Australia, indicate that congenital hypothyroidism affects 1 in 3,000 to 4,000 newborns. For reasons that remain unclear, congenital hypothyroidism affects more than twice as many females as males. What genes are related to congenital hypothyroidism?Mutations in the DUOX2, PAX8, SLC5A5, TG, TPO, TSHB, and TSHR genes cause congenital hypothyroidism. Gene mutations cause the loss of thyroid function in one of two ways. Mutations in the PAX8 gene and some mutations in the TSHR gene prevent or disrupt the normal development of the thyroid gland before birth. Mutations in the DUOX2, SLC5A5, TG, TPO, and TSHB genes prevent or reduce the production of thyroid hormones, even though the thyroid gland is present. Mutations in other genes that have not been well characterized may also cause congenital hypothyroidism. How do people inherit congenital hypothyroidism?Most cases of congenital hypothyroidism are sporadic, which means they occur in people with no history of the disorder in their family. An estimated 15 to 20 percent of cases are inherited. Many inherited cases are autosomal recessive, which means two copies of the gene in each cell are altered. Most often, the parents of a child with congenital hypothyroidism are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder. Some inherited cases (those with a mutation in the PAX8 gene or certain TSHR mutations) have an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
Source: National Institutes of Health
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Scientists at University of Pisa discuss research in congenital hypothyroidism in children
2007 AUG 14 -- Current study results from the report, "Genetic analysis of the PAX8 gene in children with congenital hypothyroidism and dysgenetic or eutopic thyroid glands: identification of a novel sequence variant," have been published. In this recent report, researchers in Pisa, Italy conducted a study "To analyse the coding region of PAX8 in individuals with congenital (CH) or post neonatal hypothyroidism due to dysgenetic (TD) or eutopic thyroid glands. AND Forty-three children with CH and TD (13 agenesis, 23 ectopia, and seven hypoplasia), one subject with post neonatal onset of hypothyroidism and thyroid ectopia, 15 children with CH and eutopic thyroid glands and six euthyroid adults with thyroid hemiagenesis were enrolled as cases, along with 120 healthy individuals as controls. Exons 2-8 of the PAX8 were directly sequenced." "HeLa and HEK293 cells were transfected with PAX8 wild-type (PAX8-WT), mutant PAX8, p300, thyroid transcription factor 1 (TTF-1) and thyroglobulin promoter pGL3 (TG prom-pGL3). Synergism of TTF-1 with PAX8-WT vs. mutant and activity of PAX8-WT vs. mutant in accompaniment with p300 on TG prom-pGL3 were also assessed. The luminescence produced by PAX8-WT and mutant PAX8 was measured. Among patients and controls only a 15-year-old girl with thyroid ectopia showed a heterozygous transition of cytosine to thymine at position 674 in exon 6, which changed a conserved threonine at position 225 to methionine (PAX8-T225M). Her father and sister harboured PAX8-T225M without abnormal thyroid phenotypes. PAX8-T225M and PAX8-WT similarly increased luciferase activity and had a similar synergistic effect with TTF-1. At 500 ng p300, however, PAX8-T225M could not significantly increase TG promoter activity when compared to PAX8-T225M alone, while PAX8-WT +500 ng p300 induction was significantly higher than PAX8-WT alone (p <0.001). Cotransfection of TTF-1 together with PAX8-T225M resulted in rescuing of the lack of synergism with p300. PAX8 mutations in congenital hypothyroidism due to dysgenetic or orthotopic thyroid glands are rare," wrote M. Tonacchera and colleagues, University of Pisa. The researchers concluded: "PAX8-T225M is probably a rare variant." Tonacchera and colleagues published their study in Clinical Endocrinology (Genetic analysis of the PAX8 gene in children with congenital hypothyroidism and dysgenetic or eutopic thyroid glands: identification of a novel sequence variant. Clinical Endocrinology, 2007;67(1):34-40). For additional information, contact M. Tonacchera, Centro di Eccellenza AmbiSEN, Dipartimento di Endocrinologia e Metabolismo, Universita di Pisa, Pisa, Italy. Publisher contact information for the journal Clinical Endocrinology is: Blackwell Publishing Ltd., 9600 Garsington Rd., Oxford OX4 2DG, Oxon, England. Keywords: Italy, Pisa, Clinical Endocrinology, Congenital Hypothyroidism, Endocrinology, Genetics. This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.
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