Novel missense mutation in the CASR gene in a Chinese family with familial hypocalciuric hypercalcemia.
BACKGROUND
Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder characterized by asymptomatic and non-progressive hypercalcemia resulting from loss-of-function mutations of the CASR (calcium-sensing receptor) gene located on chromosome 3, or from mutations in two mapped but unidentified genes located on chromosome 19.


METHODS
We report a middle-aged woman incidentally found to have FHH. To determine the molecular basis of FHH in this Chinese family, we performed direct DNA sequencing of the CASR gene of the proband.


RESULTS
We found that the proband is heterozygous for a novel missense mutation P798T, confirming the diagnosis of FHH. Family screening showed that all of the offspring with biochemical features of FHH have the P798T mutation. The mutation, P798T, is located in the third intracellular loop of the CASR, possibly affecting the downstream calcium sensing pathway and therefore inactivating the receptor function.


CONCLUSIONS
The molecular basis of FHH in a Chinese family was established. The developed mutation detection assay provides a reliable method for identifying FHH carriers.
Lam
Ching-Wan
CW
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China. ching-wanlam@cuhk.edu.hk
Lee
Ka-Fai
KF
Chan
Angel On-Kei
AO
Poon
Priscilla Miu-Kuen
PM
Law
Tak-Yin
TY
Tong
Sui-Fan
SF
D044466:Asian People; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D044169:Receptors, Calcium-Sensing / Q000737:chemistry / Q000235:genetics*
C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing