Linked Life Data

9916809

Source:http://linkedlifedata.com/resource/pubmed/id/9916809

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-2-10
pubmed:abstractText
Keutel syndrome (KS, MIM 245150) is an autosomal recessive disorder characterized by abnormal cartilage calcification, peripheral pulmonary stenosis and midfacial hypoplasia. A genome search using homozygosity mapping provided evidence of linkage to chromosome 12p12.3-13.1 (maximum multipoint lod score, 4.06). MGP was a candidate on the basis of its localization to this chromosomal region and the known function of its protein. MGP maps to chromosome 12p near D12S363. Human MGP is a 10-kD skeletal extracellular matrix (ECM) protein that consists of an 84-aa mature protein and a 19-aa transmembrane signal peptide. It is a member of the Gla protein family, which includes osteocalcin, another skeletal ECM protein, and a number of coagulation factors (factors II, VII, IX, X and proteins S and C). All members of this family have glutamic acid residues modified to gamma-carboxyglutamic acids (Gla) by a specific gamma-carboxylase using vitamin K as a cofactor. The modified glutamic acid residues of Gla proteins confer a high affinity for mineral ions such as calcium, phosphate and hydroxyapatite crystals, the mineral components of the skeletal ECM. The pattern and tissue distribution of Mgp expression in mice suggest a role for Mgp in regulating ECM calcification. Mglap-deficient mice (Mglap-/-) have been reported to have inappropriate calcification of cartilage. Mutational analysis of MGP in three unrelated probands identified three different mutations: c.69delG, IVS1-2A-->G and c.113T-->A. All three mutations predict a non-functional MGP. Our data indicate that mutations in MGP are responsible for KS and confirm its role in the regulation of extracellular matrix calcification.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
142-4
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome.
pubmed:affiliation
Department of Paediatrics, Royal Free and University College Medical School, The Rayne Institute, London, UK. p.munroe@ucl.ac.uk
pubmed:publicationType
Journal Article