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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2001-10-22
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pubmed:abstractText |
We studied family members of a large kindred expressing both familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT) and found, by PCR amplification of the extracellular calcium-sensing receptor (CASR) gene exons and flanking intronic sequences, that FHH individuals were heterozygous for a g to t substitution in the last nucleotide of intron 2 (IVS2-1G>T). Defects in messenger RNA splicing were investigated by illegitimate transcription of the CASR gene in lymphoblastoid cells from an FHH affected individual, as well as by transfection of a CASR minigene harboring this mutation into HEK293 cells. The mutation resulted predominantly in exon III skipping causing a shift in exon IV reading frame and introduction of a premature stop codon leading to a predicted truncated protein of 153 amino acids. Interestingly, it was noted that exon III splicing is not 100% efficient in parathyroid, thyroid, and kidney; an exon III-deleted transcript is produced approximately 15% of the time. This is the first description of a splice site mutation in the CASR gene and provides an explanation of the clinical phenotype of the patients.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1098-1004
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2001 Wiley-Liss, Inc.
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pubmed:issnType |
Electronic
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
411-21
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11668634-Alternative Splicing,
pubmed-meshheading:11668634-Base Sequence,
pubmed-meshheading:11668634-Cell Line,
pubmed-meshheading:11668634-Codon, Nonsense,
pubmed-meshheading:11668634-DNA Mutational Analysis,
pubmed-meshheading:11668634-Exons,
pubmed-meshheading:11668634-Female,
pubmed-meshheading:11668634-Humans,
pubmed-meshheading:11668634-Hypercalcemia,
pubmed-meshheading:11668634-Hyperparathyroidism,
pubmed-meshheading:11668634-Infant, Newborn,
pubmed-meshheading:11668634-Introns,
pubmed-meshheading:11668634-Male,
pubmed-meshheading:11668634-Mutation,
pubmed-meshheading:11668634-Nuclease Protection Assays,
pubmed-meshheading:11668634-Open Reading Frames,
pubmed-meshheading:11668634-Pedigree,
pubmed-meshheading:11668634-RNA, Messenger,
pubmed-meshheading:11668634-RNA Splice Sites,
pubmed-meshheading:11668634-Receptors, Calcium-Sensing,
pubmed-meshheading:11668634-Receptors, Cell Surface,
pubmed-meshheading:11668634-Sequence Deletion,
pubmed-meshheading:11668634-Transcription, Genetic,
pubmed-meshheading:11668634-Transfection
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pubmed:year |
2001
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pubmed:articleTitle |
An acceptor splice site mutation in the calcium-sensing receptor (CASR) gene in familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.
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pubmed:affiliation |
Department of Medicine, McGill University and Royal Victoria Hospital, Montreal, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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