Linked Life Data

21642377

Source:http://linkedlifedata.com/resource/pubmed/id/21642377

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-7-15
pubmed:abstractText
Sporadic primary hyperparathyroidism (PHPT), one of the most common endocrine disorders, is characterized by hypercalcemia and elevated PTH levels. The majority of cases are caused by a benign parathyroid adenoma, but somatic or de novo germ-line mutations that lead to adenoma formation have only been identified in few glands. GCMB is a parathyroid-specific transcription factor, which causes hypoparathyroidism when inactivated on both parental alleles or when a dominant-negative, heterozygous mutation is present. It is overexpressed in some parathyroid adenomas, and we therefore tested the hypothesis that GCMB mutations can be a cause of parathyroid adenomas. Nucleotide sequence analysis was performed on all coding exons and exon-intron borders of GCMB in 30 sporadic parathyroid adenomas and we identified several known polymorphisms that were either heterozygous or homozygous. In addition, one of the 30 investigated glands revealed a novel heterozygous missense mutation, c.1144G>A, which introduced methionine at position 382 for valine (V382M), a conserved amino acid residue. Western blot analysis using mutant GCMB (GCMB-V382M) from lysates of transiently transfected DF-1 fibroblasts, luciferase assays using extracts from these cells, and electrophoretic mobility assays failed to reveal differences between wild-type and mutant GCMB in expression level, transactivational capacity, and DNA-binding ability. Furthermore, pulse-chase experiments demonstrated no difference in half-life of wild-type and mutant protein. We conclude that mutations in the transcription factor GCMB do not seem to play a major role in the pathogenesis of PHPT.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1479-6805
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
210
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
165-71
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Mutational analysis of GCMB, a parathyroid-specific transcription factor, in parathyroid adenoma of primary hyperparathyroidism.
pubmed:affiliation
Endocrine Unit Pediatric Nephrology Unit, Massachusetts General Hospital and Harvard Medical School, Thier 1051, 55 Fruit Street, Boston, Massachusetts 02114, USA. mmannstadt@partners.org
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural