Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five families with familial inherited TSH deficiency, reported to date, were examined for the TSH beta gene at the nucleotide level. The first family carries a single base substitution in the 29th codon which lies in the so-called CAGYC region; GCA (glycine) is replaced by AGA (arginine). This substitution induces conformational changes of the beta-polypeptide which make it unable to associate with the alpha-subunit. This mutation generates a new cleavage site for a restriction endonuclease MaeI, a new marker that can be used for DNA diagnosis. The second and third families were found to carry the same nucleotide substitution. Also, all three families were associated with an additional single base substitution in intron 2 as a polymorphic change, suggesting that these three families may have originated from the same single founder from Shikoku Island in Japan. The nucleotide sequence from the fourth and fifth families showed no alterations in the TSH beta gene from the about -200 basepair up-stream region to the polyadenylation site.
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PMID:Deoxyribonucleic acid analyses of five families with familial inherited thyroid stimulating hormone deficiency. 240 10

We have recently described a mouse pituitary tumor line, MGH 101A which is derived from a TSH-producing thyrotropic tumor line and now produces only the alpha-subunit of the glycoprotein hormones. In these studies, we have investigated the mechanism for the lack of TSH beta subunit expression in MGH 101A, as well as the failure of triiodothyronine (T3) to regulate alpha-subunit. Southern blot analysis of restriction endonuclease-digested DNA from MGH 101A tumors indicates the presence of a TSH beta gene and an alpha-subunit gene indistinguishable from those in a TSH-producing tumor (TtT 97). In MGH 101A tumors, however, TSH beta gene transcription was minimal (4 +/- 2 ppm) relative to alpha-subunit (283 +/- 29 ppm) and there was no significant difference in transcription after T3 treatment. In contrast, TtT 97 tumors had nearly equal rates of alpha-subunit (375 +/- 25 ppm) gene transcirption, and T3 respectively. The MGH 101A suppressed the transcription of alpha-subunit and TSH beta genes by 76% and 87%, respectively. The MGH 101A tumor contained T3 receptors with a binding affinity (1.54 X 10-10M) similar to receptors on TtT 97 tumors (1.78 X 10-10M), but at a lower concentration (2800 vs. 4000 sites/cell). We conclude that the absence of TSH beta production in MGH 101A tumors is not due to the absence of the TSH beta gene, but perhaps to some other modification of the gene structure. This could also explain the failure of MGH 101A tumors to respond to T3, since they do contain T3 receptors of normal affinity.
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PMID:A non-responsive alpha-secreting thyrotropic tumor contains T3 receptors and a TSH beta gene. 300 38

Genomic DNA from 18 patients with combined pituitary hormone deficiency was screened for 2-bp deletion (A301,G302) in PROP1 gene by BcgI restriction endonuclease analysis of PCR-amplified exon 2 gene fragments. Two unrelated female patients were homozygous for this 2-bp deletion. Patient 1 presented at 8.8 yr with severe short stature (-2.9 SD score), slightly enlarged sella turcica at x-rays, and diffusely enlarged pituitary gland (height, 8 mm vs. 4.5 +/- 0.6 mm in matched controls) with hyperintense enhanced signal at T1 weighted image at coronal and sagittal views at magnetic resonance imaging (MRI). MRI repeated at age 15 yr revealed a marked reduction of pituitary height (2 mm vs. 5.3 +/- 0.8 mm in matched controls). Patient 2 presented at 27 yr with short stature (-5.5 SD score) without pubertal development, normal sella turcica, and a pituitary gland of reduced size (height, 5 mm vs. 6.1 +/- 0.3 mm in matched controls) of normal intensity at MRI. Both patients had normal pituitary stalk and normally located neurohypophysis. Hormonal features were characterized by GH, TSH, PRL, LH, and FSH deficiencies. Patient 1 had normal cortisol secretion at 8.8 yr, and at 16.6 yr had developed partial cortisol deficiency, whereas patient 2 maintained normal cortisol secretion at 28.4 yr. We conclude that 1) a large sella turcica and an enlarged pituitary anterior lobe with hyperintense enhanced signal at T1 at MRI can be suggestive of PROP1 deficiency; 2) pituitary morphology can change during follow-up of patients with PROP1 gene mutation; and 3) hormonal deficiencies could include the adrenal axis.
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PMID:Longitudinal hormonal and pituitary imaging changes in two females with combined pituitary hormone deficiency due to deletion of A301,G302 in the PROP1 gene. 1008 75

In the present study, we report a Thai female with a de novo mutation in thyroid hormone receptor-beta (TRbeta) gene causing resistance to thyroid hormone (RTH). The patient was a 19 year-old woman who presented with goiter for 1 year. Except for tachycardia she had no signs of thyrotoxicosis. Previously she was treated with propylthiouracil based on the diagnosis of thyrotoxicosis for 9 months and her goiter became more enlarged. The patient was the only child of the family. Her parents were alive and healthy, and did not have goiter or any other thyroid diseases. Physical examination revealed no sign of thyrotoxicosis. Her thyroid gland was diffusely enlarged with an estimated weight of 100 gm. Laboratory determinations revealed elevated free T4, T3 and nonsuppressed TSH levels. Exon 9 of the TRbeta gene was amplified by PCR and the DNA sequence was determined by dye terminator cycle sequencing. Heterozygous point mutation in which T was replaced by C was detected at position 1274 (TTG to TCG) corresponding to a leucine to serine substitution at codon 330. No mutation was found in the parents indicating that the mutation was de novo. The nucleotide change created a restriction site for Taq 1 restriction endonuclease and the mutation was confirmed by restriction fragments length polymorphism. The same nucleotide change has been reported in a family with RTH.
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PMID:A de novo L330S point mutation in thyroid hormone receptor beta gene in a Thai female with resistance to thyroid hormone. 1072 59

We identified a new nonsense mutation of the TSH-beta subunit gene responsible for a severe isolated TSH deficiency in two children from the same consanguineous kindred. These affected children are homozygous for a C-to-T transition at nucleotide 654 of the TSH-beta subunit gene, leading to the conversion of a glutamine (CAG) to a premature stop codon (TAG) in the codon 49 (Q49X). The resulting nascent peptide does not contain the seat belt region (amino acid residues 88-105), a TSH-beta subunit region crucial for the dimerization with the alpha-subunit, and, hence, the correct secretion of the mature TSH heterodimer is hampered. Free T(3), free T(4) as well as basal TSH levels were extremely low in both affected individuals and, importantly, TRH stimulations failed to increase serum TSH, but not PRL, confirming isolated TSH deficiency. Using the new StyI endonuclease restriction site generated by the mutation, we confirmed that the affected children were homozygous for the Q49X TSH-beta mutation whereas their unaffected parents as well as their unaffected brother were heterozygous. Consequently, this isolated TSH deficiency follows an autosomal recessive mode of inheritance.
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PMID:New autosomal recessive mutation of the TSH-beta subunit gene causing central isolated hypothyroidism. 1154 95

Apurinic/apyrimidinic endonuclease APE/Ref-1 is a multifunctional protein provided with DNA repair, transcription-factor regulation and anti-apoptotic activities. We have previously reported that, in thyroid cells, TSH regulates both the synthesis and nuclear translocation of APE/Ref-1. We have also shown that nuclear levels of this protein are reduced both in thyroid carcinoma tissues and cell lines. In the present study, APE/Ref-1 expression and cellular localization were analysed by Western blot in hyperfunctioning thyroid nodules from patients with toxic adenoma and/or toxic multinodular goiter. The total content of APE/Ref-1 protein was increased in the majority of the hyperfunctioning tissues with respect to normal adjacent tissue. There was also an increase in the nuclear levels of APE/Ref-1, suggesting enhanced cytoplasm-to-nucleus translocation of the protein in addition to its increased rate of synthesis. These results demonstrate that the phenomenon of nuclear translocation of APE/Ref-1 hypothesized on the basis of cell culture experiments does actually occur in vivo. Together with previous observations in thyroid carcinomas and tumoral cell lines, our findings suggest a two-stage model of APE/Ref-1 behaviour during malignant thyrocyte transformation: an early stage characterized by simple hyperplasia and upregulation of APE/Ref-1 in the nuclear compartment of the cell and a later stage in which nuclear levels of the protein drop to below-normal levels as the cell becomes progressively undifferentiated.
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PMID:APE/Ref-1 is increased in nuclear fractions of human thyroid hyperfunctioning nodules. 1224 29