Linked Life Data

8432414

Source:http://linkedlifedata.com/resource/pubmed/id/8432414

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1993-3-16
pubmed:abstractText
INSR gene mutations have been described in multiple individuals with extreme insulin resistance, but the INSR gene has not been implicated in familial NIDDM. We previously have screened members of 18 familial NIDDM pedigrees for mutations in exons encoding the tyrosine kinase domain of the INSR gene (exons 13-21) by SSCP. That analysis initially detected only patterns consistent with silent polymorphisms, but on direct sequence analysis of exon 17 we detected a Met-for-Val substitution at position 985 in 1/18 pedigrees. We confirmed the substitution by sequence analysis of subcloned, PCR-amplified DNA from two pedigree members and by hybridization to labeled primers for the normal and mutant sequences. We did not find the mutation in any other individuals. Pedigree members were typed for presence or absence of the Met985 substitution by hybridization of PCR-amplified exon 17 DNA to allele-specific oligonucleotide probes, and typing was confirmed by segregation of INSR haplotypes and by SSCP analysis. The substitution was present in 3 NIDDM individuals in 3 generations, including a lean individual with onset at age 24. The substitution was present in only 50% of NIDDM siblings in generation 2, however. To determine the clinical effect of the Met985 substitution, we compared the 5 nondiabetic pedigree members who carried the mutation with the 9 nondiabetic pedigree members without the mutation and with 266 members of other pedigrees. Fasting and 1-h postglucose insulin levels were not different between carriers and noncarriers (fasting, 71.4 pM vs. 74.5 pM; 1-h, 381 pM vs. 354 pM), even after correction for age, sex, and BMI.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
429-34
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Methionine for valine substitution in exon 17 of the insulin receptor gene in a pedigree with familial NIDDM.
pubmed:affiliation
Department of Medicine, Veterans Affairs Medical Center, Salt Lake City, UT 84148.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't