Linked Life Data

11156372

Source:http://linkedlifedata.com/resource/pubmed/id/11156372

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2001-1-11
pubmed:abstractText
Most pheochromocytomas are sporadic but about 10% are though to be hereditary. Although the etiology of most inherited pheochromocytoma is well known, little is known about the etiology of the more common sporadic tumor. Recently, germ-line mutations of SDHD, a mitochondria complex II gene, were found in patients with hereditary paraganglioma. We sought to determine whether SDHD plays a role in the development of sporadic pheochromocytomas and performed a mutation and deletion analysis of SDHD. Among 18 samples, we identified 4 heterozygous sequence variants (3 germ-line, 1 somatic). One germ-line SDHD mutation IVS1+2T>G (absent among 78 control alleles) is predicted to cause aberrant splicing. On reinvestigation, this patient was found to have a tumor of the carotid body, which was likely a paraganglioma. Another patient with malignant, extra-adrenal pheochromocytoma was found to have germ-line c.34G> A (G12S). However, this sequence variant was also found in 1 of 78 control alleles. The third, germ-line nonsense mutation R38X was found in a patient with extra-adrenal pheochromocytoma. The only somatic heterozygous mutation, c.242C>T (P81L), has been found in the germ line of two families with hereditary paraganglioma and is conserved among four eukaryotic multicellular organisms. Hence, this mutation is most likely of functional significance too. Overall, loss of heterozygosity in at least one of the two markers flanking SDHD was found in 13 tumors (72%). All of the tumors that already harbored intragenic SDHD mutations, whether germ-line or somatic, also had loss of heterozygosity. Our results indicate that SDHD plays a role in the pathogenesis of pheochromocytoma. Given the minimum estimated germline SDHD mutation frequency of 11% (maximum estimate up to 17%) in this set of apparently sporadic pheochromocytoma cases and if these data can be replicated in other populations, our observations might suggest that all such patients be considered for SDHD mutation analysis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6822-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11156372-Adolescent, pubmed-meshheading:11156372-Adrenal Gland Neoplasms, pubmed-meshheading:11156372-Adult, pubmed-meshheading:11156372-Aged, pubmed-meshheading:11156372-Alleles, pubmed-meshheading:11156372-Codon, Nonsense, pubmed-meshheading:11156372-DNA Mutational Analysis, pubmed-meshheading:11156372-Electron Transport Complex II, pubmed-meshheading:11156372-Female, pubmed-meshheading:11156372-Genetic Markers, pubmed-meshheading:11156372-Germ-Line Mutation, pubmed-meshheading:11156372-Heterozygote, pubmed-meshheading:11156372-Humans, pubmed-meshheading:11156372-Loss of Heterozygosity, pubmed-meshheading:11156372-Male, pubmed-meshheading:11156372-Middle Aged, pubmed-meshheading:11156372-Mitochondria, pubmed-meshheading:11156372-Multienzyme Complexes, pubmed-meshheading:11156372-Mutation, pubmed-meshheading:11156372-Oxidoreductases, pubmed-meshheading:11156372-Paraganglioma, pubmed-meshheading:11156372-Pheochromocytoma, pubmed-meshheading:11156372-Succinate Dehydrogenase
pubmed:year
2000
pubmed:articleTitle
Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma.
pubmed:affiliation
Department of Internal Medicine, The Ohio State University, Columbus 43210, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't