scholarly journals Novel mutation in MCT8 gene in a Brazilian boy with thyroid hormone resistance and severe neurologic abnormalities

2011 ◽  
Vol 55 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Hamilton Cabral de Menezes Filho ◽  
Suemi Marui ◽  
Thais Della Manna ◽  
Ester Saraiva Brust ◽  
Vanessa Radonsky ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Novel Mutation ◽  
Normal Growth ◽  
Signs And Symptoms ◽  
Serum Levels ◽  
High Serum ◽  
Laboratory Evaluation ◽  
Coding Region ◽  
Free T4 ◽  
Exon 1

MCT8 is a cellular transporter of thyroid hormones important in their action and metabolization. We report a male patient with the novel inactivating mutation 630insG in the coding region in exon 1 of MCT8. He was characterized clinically by severe neurologic impairment (initially with global hypotonia, later evolving with generalized hypertonia), normal growth during infancy, reduced weight gain, and absence of typical signs and symptoms of hypothyroidism, while the laboratory evaluation disclosed elevated T3, low total and free T4, and mildly elevated TSH serum levels. Treatment with levothyroxine improved thyroid hormone profile but was not able to alter the clinical picture of the patient. These data reinforce the concept that the role of MCT8 is tissue-dependent: while neurons are highly dependent on MCT8, bone tissue, adipose tissue, muscle, and liver are less dependent on MCT8 and, therefore, may suffer the consequences of the exposition to high serum T3 levels.

scholarly journals Syndrome of Reduced Sensitivity to Thyroid Hormones: Two Case Reports and a Literature Review

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Anastasios Anyfantakis ◽  
Dimitrios Anyfantakis ◽  
Irene Vourliotaki
Keyword(s):  
Thyroid Hormone ◽  
Multinodular Goiter ◽  
Target Genes ◽  
Case Reports ◽  
Serum Levels ◽  
Free T4 ◽  
Laboratory Findings ◽  
Toxic Multinodular Goiter ◽  
High Doses ◽  
Primary Hyperthyroidism

Resistance to thyroid hormone (RTH) is an extremely rare dominantly inherited condition of impaired tissue responsiveness to thyroid hormone (TH). Most patients with RTH have mutations in the gene that encodes theβisoform of the receptor of thyroid hormone (THR-βgene). Mutant receptors are unable to activate or repress target genes. The majority of them are asymptomatic or rarely have hypo- or hyperthyroidism. RTH is suspected by the finding of persistent elevation of serum levels of free T3 (FT3) and free T4 (FT4) and nonsuppressed TSH. We present two cases of RTH diagnosed after total thyroidectomy. The first patient was initially diagnosed with primary hyperthyroidism due to toxic multinodular goiter. The second patient had undergone thyroidectomy for multinodular goiter 16 years before diagnosis of RTH. After thyroidectomy, although on relatively high doses of levothyroxine, both of them presented with the laboratory findings of RTH. Genetic analysis revealed RTH.

Relationship between Thyroid Hormones and Plasma D-dimer Levels

1998 ◽  
Vol 79 (01) ◽  
pp. 99-103 ◽  
Author(s):  
Eric Bruckert ◽  
Annick Ankri ◽  
Isabel Beucler ◽  
Philippe Giral ◽  
Gérard Turpin ◽  
...  
Keyword(s):  
Physiological Role ◽  
Correlation Coefficients ◽  
Plasminogen Activator Inhibitor ◽  
Serum Levels ◽  
Multivariate Regression Analysis ◽  
High Serum ◽  
Primary Hypothyroidism ◽  
Factor Vii ◽  
Free T4 ◽  
Pai 1

SummaryHigh serum levels of cholesterol and triglycerides are risk factors for coronary heart disease and are strongly related to several haemostatic parameters. Thyroid disorders are a frequent feature in hyperlipidemic patients and are also associated with a variety of haemostatic abnormalities. Therefore, we analysed the relationships between free T4 (fT4) levels and Factor VII and VIII activities (FVIIc and FVIIIc), D-Dimers (DDI) and Plasminogen Activator Inhibitor type 1 (PAI-1), in a group of 472 healthy patients referred for hyperlipidemia.Fourty patients were found to have primary hypothyroidism. A negative correlation was found in the whole study population between fT4 and DDI (p = 0.0001, r = –0.21) and the same results were found after exclusion of the patients with fT4 below the normal range (p = 0.0007, r = –0.17). In a multivariate regression analysis, the relationship between DDI and fT4 was independent of age, Body Mass Index (BMI), gender and total cholesterol. Less impressive correlation coefficients were found with FVIIc (r = –0.10), FVIIIc (r = –0.09) and PAI-1 (r = –0.09).These results suggest that fT4 may play a physiological role in the regulation of the haemostatic equilibrium in hyperlipidemic patients and that low levels of fT4 are associated with a hypercoagulable state.

scholarly journals Complete Androgen Insensitivity Caused by a New Frameshift Deletion of Two Base Pairs in Exon 1 of the Human Androgen Receptor Gene1

1999 ◽  
Vol 84 (5) ◽  
pp. 1751-1753 ◽  
Author(s):  
Brigitta Thiele ◽  
Wolfgang Weidemann ◽  
Doris Schnabel ◽  
Gabriela Romalo ◽  
Hans-Udo Schweikert ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Stop Codon ◽  
Novel Mutation ◽  
Reductase Activity ◽  
Receptor Gene ◽  
Premature Stop Codon ◽  
Androgen Receptor Gene ◽  
Coding Region ◽  
Androgen Insensitivity ◽  
Exon 1

We describe a novel mutation in exon 1 of the androgen receptor gene in a patient with complete androgen insensitivity (CAIS). Endocrine findings were typical for androgen insensitivity (testosterone serum levels in the upper limit of normal males and increased LH serum concentrations). Biochemical investigations in cultured genital skin fibroblasts of the patient showed a normal 5α-reductase activity but a complete absence of androgen binding. Western blot analysis revealed no detectable protein product. Sequence analysis of the entire coding region of the androgen receptor gene resulted in the identification of a 2-bp deletion in codon 472, causing frameshift and introduction of a premature stop codon 27 codons downstream of the mutation.

scholarly journals Thyroid Hormone Concentrations, Disease, Physical Function, and Mortality in Elderly Men

2005 ◽  
Vol 90 (12) ◽  
pp. 6403-6409 ◽  
Author(s):  
Annewieke W. van den Beld ◽  
Theo J. Visser ◽  
Richard A. Feelders ◽  
Diederick E. Grobbee ◽  
Steven W. J. Lamberts
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Physical Function ◽  
Grip Strength ◽  
High Serum ◽  
Healthy Adults ◽  
Elderly Men ◽  
Normal Range ◽  
Free T4 ◽  
Low T3

Context: Physiological changes in thyroid hormone concentrations might be related to changes in the overall physical function in the elderly. Objective: We determined to what extent thyroid hormone concentrations are related to physical function and mortality in elderly men. Design: A longitudinal population study (the Zoetermeer study) was conducted. Mortality was registered in the subsequent 4 yr. Participants: Four hundred three independently and ambulatory living men (aged 73–94 yr) participated. Main Outcome Measures: The study examined the association between serum thyroid hormones and parameters of physical function as well as the association with mortality. Methods: TSH, free T4 (FT4) total T4, T3, rT3, and T4-binding globulin were measured. Physical function was estimated by the number of problems in activities of daily living, a measure of physical performance score (PPS), leg extensor strength and grip strength, bone density, and body composition. Results: Serum rT3 increased significantly with age and the presence of disease. Sixty-three men met the biochemical criteria for the low T3 syndrome (decreased serum T3 and increased serum rT3). This was associated with a lower PPS, independent of disease. Furthermore, higher serum FT4 (within the normal range of healthy adults) and rT3 (above the normal range of healthy adults) were related with a lower grip strength and PPS, independent of age and disease. Isolated low T3 was associated with a better PPS and a higher lean body mass. Low FT4 was related to a decreased risk of 4-yr mortality. Conclusions: In a population of independently living elderly men, higher FT4 and rT3 concentrations are associated with a lower physical function. High serum rT3 may result from a decreased peripheral metabolism of thyroid hormones due to the aging process itself and/or disease and may reflect a catabolic state. Low serum FT4 is associated with a better 4-yr survival; this may reflect an adaptive mechanism to prevent excessive catabolism.

scholarly journals An unusual case of schwannomatosis with bilateral maxillary sinus schwannomas and a novel SMARCB1 gene mutation

2016 ◽  
Vol 24 (1) ◽  
pp. 160-166 ◽  
Author(s):  
Jamie Toms ◽  
Jason Harrison ◽  
Hope Richard ◽  
Adrienne Childers ◽  
Evan R. Reiter ◽  
...  
Keyword(s):  
Maxillary Sinus ◽  
Unusual Case ◽  
Novel Mutation ◽  
Signs And Symptoms ◽  
Neurofibromatosis Type ◽  
The Body ◽  
Benign Tumors ◽  
Exon 1 ◽  
Multiple Schwannomas

Schwannomas are benign tumors that arise from Schwann cells in the peripheral nervous system. Patients with multiple schwannomas without signs and symptoms of neurofibromatosis Type 1 or 2 have the rare disease schwannomatosis. Tumors in these patients occur along peripheral nerves throughout the body. Mutations of the SMARCB1 gene have been described as one of the predisposing genetic factors in the development of this disease. This report describes a patient who was observed for 6 years after having undergone removal of 7 schwannomas, including bilateral maxillary sinus schwannomas, a tumor that has not been previously reported. Genetic analysis revealed a novel mutation of c.93G>A in exon 1 of the SMARCB1 gene.

scholarly journals A novel mutation of thyroid hormone receptor beta (I431V) impairs corepressor release, and induces thyroid hormone resistance syndrome

2008 ◽  
Vol 52 (8) ◽  
pp. 1304-1312 ◽  
Author(s):  
Monalisa Ferreira Azevedo ◽  
Gustavo Barcelos Barra ◽  
Ligiane Dantas de Medeiros ◽  
Luiz Alberto Simeoni ◽  
Luciana Ansaneli Naves ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Novel Mutation ◽  
Plasma Concentrations ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Free T4 ◽  
Functional Studies ◽  
Receptor Beta

Resistance to thyroid hormone (RTH) is a rare disorder characterized by variable tissue hyporesponsiveness to thyroid hormone, usually caused by mutations in the thyroid hormone receptor beta (TRβ). We describe a large Brazilian family harboring a novel mutation affecting TRβ gene and inducing RTH. A 14-year-old girl was found to have elevated free T4 and free T3 plasma concentrations in coexistence with unsuppressed TSH and a questionable goiter. The diagnosis of RTH was verified by identification of a novel mutation (I431V) in the TRβ gene. Sixteen asymptomatic relatives of the proposita are also affected by the mutation. Functional studies showed that I431V mutation exerts dominant-negative effect on wild type TRβ, mainly by impairment of ligand-dependent release of corepressor SMRT. The presence of this mutation reduces potency, but does not affect efficacy of thyroid hormone action, in accordance with the clinical picture of eumetabolism of the affected individuals.

scholarly journals A Case of Resistance to Thyroid Hormone with Chronic Thyroiditis: Discovery of a Novel Mutation (I54V)

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
I. Kammoun ◽  
C. Bouzid ◽  
H. Kandara ◽  
L. Ben Salem ◽  
Z. Turki ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Novel Mutation ◽  
Positive Sequence ◽  
Thyroid Peroxidase ◽  
Free T4 ◽  
Chronic Thyroiditis ◽  
Resistance To Thyroid Hormone ◽  
Upper Limits ◽  
Receptor Beta

Resistance to thyroid hormone (RTH) is a rare disorder characterized by variable tissue hyporesponsiveness to thyroid hormone, usually caused by mutations in the thyroid hormone receptor beta (TRβ). It has been reported that the serum of patients with RTH is free of auto-antibodies against thyroglobulin (Tg) and thyroid peroxidase (TPO), except in rare cases where coincidental autoimmune thyroiditis is also present. We describe a 13-year-old girl with chronic thyroiditis and RTH. This patient had increased plasma free T3, free T4 at the upper limits with unsuppressed TSH. She had peripheral manifestations of thyroid hormone excess, hypertension and growth acceleration. Anti-TPO antibodies were positive. Sequence analysis of the TRβgene was performed and revealed a novel mutation I54V in exon 4. The same mutation was also found in the mother and two asymptomatic sisters. The clinical presentation of our patient is not habitual in RTH because growth retardation is frequently reported in this syndrome. The association between RTH and thyroiditis complicate the management of the hypothyroidism.

Van Wyk-Grumbach syndrome with hemangioma in an infant

2018 ◽  
Vol 31 (9) ◽  
pp. 1057-1060
Author(s):  
Moumita Biswas ◽  
Malay Kumar Sinha ◽  
Mrinal Kanti Das ◽  
Sumantra Sarkar
Keyword(s):  
Thyroid Hormone ◽  
Congenital Hypothyroidism ◽  
Hormone Replacement ◽  
Signs And Symptoms ◽  
Bone Age ◽  
Infantile Hemangioma ◽  
Thyroid Stimulating Hormone ◽  
High Serum ◽  
Primary Hypothyroidism ◽  
Thyroid Hormone Replacement

Abstract Background Van Wyk-Grumbach syndrome (VWGS) is characterized by juvenile primary hypothyroidism, delayed bone age and isosexual incomplete precocious puberty with reversal to the prepubertal state following thyroid hormone replacement. Case presentation In this case, an 18-month-old girl presented with premature menarche since 9 months of age, delayed bone age and enlarged bilateral multicystic ovaries along with a superficial infantile hemangioma over the upper anterior chest. VWGS was diagnosed based on the clinical features. High serum thyroid stimulating hormone and low free thyroxine with the absence of any carpal bones in the wrist X-ray were suggestive of congenital hypothyroidism. Interestingly, the coexisting hemangioma could also play a role in the etiology of the hypothyroidism through “consumptive hypothyroidism”. Thyroid hormone replacement resulted in the complete resolution of signs and symptoms. Conclusions Untreated congenital hypothyroidism of short duration, onset of symptoms in infancy and association of an infantile hemangioma in VWGS were the unique features in our case.

Characterization of the Original Christmas Disease Mutation (Cysteine 206 → Serine): From Clinical Recognition to Molecular Pathogenesis

1992 ◽  
Vol 67 (01) ◽  
pp. 063-065 ◽  
Author(s):  
Sherryl A M Taylor ◽  
Jacalyn Duffin ◽  
Cherie Cameron ◽  
Jerome Teitel ◽  
Bernadette Garvey ◽  
...  
Keyword(s):  
Nucleotide Substitution ◽  
Novel Mutation ◽  
Factor Ix ◽  
Causative Mutation ◽  
Coding Region ◽  
Body Of Knowledge ◽  
Polymerase Chain ◽  
Splice Junctions

SummaryChristmas disease was first reported as a distinct clinical entity in two manuscripts published in 1952 (1, 2). The eponym associated with this disorder, is the surname of the first patient examined in detail and reported by Biggs and colleagues in a paper describing the clinical and laboratory features of seven affected individuals (3). This patient has severe factor IX coagulant deficiency (less than 0.01 units/ml) and no detectable circulating factor IX antigen (less than 0.01 units/ml). Coding sequence and splice junctions of the factor IX gene from this patient have been amplified in vitro through the polymerase chain reaction (PCR). One nucleotide substitution was identified at nucleotide 30,070 where a guanine was replaced by a cytosine. This mutation alters the amino acid encoded at position 206 in the factor IX protein from cysteine to serine. The non conservative nature of this substitution, the absence of this change in more than 200 previously sequenced factor IX genes and the fact that the remainder of the coding region of this gene was normal, all provide strong circumstantial evidence in favour of this change being the causative mutation in this patient. The molecular characterization of this novel mutation in the index case of Christmas disease, contributes to the rapidly expanding body of knowledge pertaining to Christmas disease pathogenesis.

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