Linked Life Data

1727829

Source:http://linkedlifedata.com/resource/pubmed/id/1727829

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1992-1-30
pubmed:abstractText
Generalized resistance to thyroid hormone is a syndrome of reduced responsiveness of target tissues to thyroid hormone. The determination of amino acid sequences of the human thyroid receptor-beta (hTR beta), deduced from cDNA sequencing, has enabled evaluation of the genetic basis for this syndrome. Distinct point mutations in the ligand-binding domain of hTR beta have been identified in affected members of unrelated families, producing single amino acid substitutions that result in products with decreased or no hormone-binding activity. Inheritance in these families was autosomal dominant. We now report the molecular basis of generalized resistance to thyroid hormone in a consanguineous family unique for its autosomal recessive mode of inheritance. Deletion of the entire coding region of both hTR beta alleles in homozygous affected members of the family was demonstrated by the failure to amplify the coding exons 3-8 by the polymerase chain reaction using primers specific for flanking intronic sequences and by the demonstration of the presence of only two noncoding exons in Southern blots hybridized with exon-specific probes. As expected, obligate heterozygotes were phenotypically normal, since, in contrast to alleles with point mutations, the deleted allele could not act in a dominant negative fashion. Survival and maintenance of a euthyroid state are presumably mediated through expression of the hTR alpha gene, present in affected subjects, and the maintenance of high thyroid hormone levels. Furthermore, the clinical manifestations were relatively more mild that those observed in a homozygous patient with a single amino acid deletion in the hTR beta gene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
49-55
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Recessive inheritance of thyroid hormone resistance caused by complete deletion of the protein-coding region of the thyroid hormone receptor-beta gene.
pubmed:affiliation
Department of Medicine, University of Chicago, Illinois 60637.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.