PMID- 11668634
OWN - NLM
STAT- MEDLINE
DCOM- 20020110
LR  - 20061115
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Linking)
VI  - 18
IP  - 5
DP  - 2001 Nov
TI  - An acceptor splice site mutation in the calcium-sensing receptor (CASR) gene in 
      familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.
PG  - 411-21
AB  - 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.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - D'Souza-Li, L
AU  - D'Souza-Li L
AD  - Department of Medicine, McGill University and Royal Victoria Hospital, Montreal, 
      Canada.
FAU - Canaff, L
AU  - Canaff L
FAU - Janicic, N
AU  - Janicic N
FAU - Cole, D E
AU  - Cole DE
FAU - Hendy, G N
AU  - Hendy GN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (Codon, Nonsense)
RN  - 0 (RNA Splice Sites)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
MH  - Alternative Splicing/*genetics
MH  - Base Sequence
MH  - Cell Line
MH  - Codon, Nonsense/genetics
MH  - DNA Mutational Analysis
MH  - Exons/genetics
MH  - Female
MH  - Humans
MH  - Hypercalcemia/*genetics
MH  - Hyperparathyroidism/*genetics
MH  - Infant, Newborn
MH  - Introns/genetics
MH  - Male
MH  - Mutation/*genetics
MH  - Nuclease Protection Assays
MH  - Open Reading Frames/genetics
MH  - Pedigree
MH  - RNA Splice Sites/*genetics
MH  - RNA, Messenger/analysis/genetics
MH  - Receptors, Calcium-Sensing
MH  - Receptors, Cell Surface/chemistry/*genetics/metabolism
MH  - Sequence Deletion/genetics
MH  - Transcription, Genetic/genetics
MH  - Transfection
EDAT- 2001/10/23 10:00
MHDA- 2002/01/11 10:01
CRDT- 2001/10/23 10:00
PHST- 2001/10/23 10:00 [pubmed]
PHST- 2002/01/11 10:01 [medline]
PHST- 2001/10/23 10:00 [entrez]
AID - 10.1002/humu.1212 [pii]
AID - 10.1002/humu.1212 [doi]
PST - ppublish
SO  - Hum Mutat. 2001 Nov;18(5):411-21. doi: 10.1002/humu.1212.