The Ca2+-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism
Identifieur interne : 002132 ( Main/Exploration ); précédent : 002131; suivant : 002133The Ca2+-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism
Auteurs : Roger L Vlie ; Hans Geir Eiken ; Jan Inge S Rheim ; H. BomanSource :
- Human Genetics [ 0340-6717 ] ; 1996-07-01.
Abstract
Abstract : Isolated autosomal dominant hypoparathyroidism is a heterogeneous disorder characterized by parathyroid hormone (PTH) deficiency, hypocalcemia and hyperphosphatemia. The candidate gene approach was used to study a large Norwegian family. The loci for the PTH gene, PTH receptor gene and RET protooncogene were excluded using dinucleotide markers and restriction fragment length polymorphism analysis. Complete cosegregation of this trait was found with the chromosomal region 3q13, using the short tandem repeat markers D3S1267, D3S1269, D3S1303, D3S1518, and RHO. This region contains the candidate locus for the Ca2+-sensing receptor (PCAR1). By single-strand conformation polymorphism (SSCP) analysis of all PCAR1 exons followed by automated sequencing, we identified a C to T transition in exon 2 (cDNA position 452) on the mutant allele in the family. The mutation predicts a substitution of Thr to Met in amino acid position 151 (T151M). A StyI restriction site created by the nucleotide substitution was used to confirm the mutation on all alleles, as well as to exclude it among 100 normal alleles (blood donors). SSCP analysis also identified a novel polymorphism of PCAR1 intron 4 (1609–88t→c) on normal alleles.The T151M mutation is located in the extracellular N-terminal domain of PCAR1, which belongs to the superfamily of G protein-coupled receptors. We suggest that this is a gain-of-function mutation that increases the sensitivity of the receptor to [Ca2+], thereby decreasing the calcium set point.
Url:
DOI: 10.1007/s004390050174
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">The Ca2+-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism</title><author><name sortKey="L Vlie, Roger" sort="L Vlie, Roger" uniqKey="L Vlie R" first="Roger" last="L Vlie">Roger L Vlie</name></author><author><name sortKey="Eiken, Hans Geir" sort="Eiken, Hans Geir" uniqKey="Eiken H" first="Hans Geir" last="Eiken">Hans Geir Eiken</name></author><author><name sortKey="S Rheim, Jan Inge" sort="S Rheim, Jan Inge" uniqKey="S Rheim J" first="Jan Inge" last="S Rheim">Jan Inge S Rheim</name></author><author><name sortKey="Boman, H" sort="Boman, H" uniqKey="Boman H" first="H." last="Boman">H. Boman</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:87D5C8251CF7D76B319D93A4CB4BB9CD43A64F44</idno><date when="1996" year="1996">1996</date><idno type="doi">10.1007/s004390050174</idno><idno type="url">https://api.istex.fr/document/87D5C8251CF7D76B319D93A4CB4BB9CD43A64F44/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002334</idno><idno type="wicri:Area/Main/Curation">002013</idno><idno type="wicri:Area/Main/Exploration">002132</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">The Ca2+-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism</title><author><name sortKey="L Vlie, Roger" sort="L Vlie, Roger" uniqKey="L Vlie R" first="Roger" last="L Vlie">Roger L Vlie</name><affiliation><wicri:noCountry code="subField">NO</wicri:noCountry></affiliation></author><author><name sortKey="Eiken, Hans Geir" sort="Eiken, Hans Geir" uniqKey="Eiken H" first="Hans Geir" last="Eiken">Hans Geir Eiken</name><affiliation><wicri:noCountry code="subField">NO</wicri:noCountry></affiliation></author><author><name sortKey="S Rheim, Jan Inge" sort="S Rheim, Jan Inge" uniqKey="S Rheim J" first="Jan Inge" last="S Rheim">Jan Inge S Rheim</name><affiliation><wicri:noCountry code="subField">NO</wicri:noCountry></affiliation></author><author><name sortKey="Boman, H" sort="Boman, H" uniqKey="Boman H" first="H." last="Boman">H. Boman</name><affiliation><wicri:noCountry code="subField">NO</wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j">Human Genetics</title><title level="j" type="abbrev">Hum Genet</title><idno type="ISSN">0340-6717</idno><idno type="eISSN">1432-1203</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="1996-07-01">1996-07-01</date><biblScope unit="volume">98</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="129">129</biblScope><biblScope unit="page" to="133">133</biblScope></imprint><idno type="ISSN">0340-6717</idno></series><idno type="istex">87D5C8251CF7D76B319D93A4CB4BB9CD43A64F44</idno><idno type="DOI">10.1007/s004390050174</idno><idno type="ArticleID">Art1</idno><idno type="ArticleID">60980129.439</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0340-6717</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract : Isolated autosomal dominant hypoparathyroidism is a heterogeneous disorder characterized by parathyroid hormone (PTH) deficiency, hypocalcemia and hyperphosphatemia. The candidate gene approach was used to study a large Norwegian family. The loci for the PTH gene, PTH receptor gene and RET protooncogene were excluded using dinucleotide markers and restriction fragment length polymorphism analysis. Complete cosegregation of this trait was found with the chromosomal region 3q13, using the short tandem repeat markers D3S1267, D3S1269, D3S1303, D3S1518, and RHO. This region contains the candidate locus for the Ca2+-sensing receptor (PCAR1). By single-strand conformation polymorphism (SSCP) analysis of all PCAR1 exons followed by automated sequencing, we identified a C to T transition in exon 2 (cDNA position 452) on the mutant allele in the family. The mutation predicts a substitution of Thr to Met in amino acid position 151 (T151M). A StyI restriction site created by the nucleotide substitution was used to confirm the mutation on all alleles, as well as to exclude it among 100 normal alleles (blood donors). SSCP analysis also identified a novel polymorphism of PCAR1 intron 4 (1609–88t→c) on normal alleles.The T151M mutation is located in the extracellular N-terminal domain of PCAR1, which belongs to the superfamily of G protein-coupled receptors. We suggest that this is a gain-of-function mutation that increases the sensitivity of the receptor to [Ca2+], thereby decreasing the calcium set point.</div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Boman, H" sort="Boman, H" uniqKey="Boman H" first="H." last="Boman">H. Boman</name><name sortKey="Eiken, Hans Geir" sort="Eiken, Hans Geir" uniqKey="Eiken H" first="Hans Geir" last="Eiken">Hans Geir Eiken</name><name sortKey="L Vlie, Roger" sort="L Vlie, Roger" uniqKey="L Vlie R" first="Roger" last="L Vlie">Roger L Vlie</name><name sortKey="S Rheim, Jan Inge" sort="S Rheim, Jan Inge" uniqKey="S Rheim J" first="Jan Inge" last="S Rheim">Jan Inge S Rheim</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002132 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002132 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:87D5C8251CF7D76B319D93A4CB4BB9CD43A64F44
|texte= The Ca2+-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism
}}
| This area was generated with Dilib version V0.6.23. |  |