OBJECTIVE: @entity74 ( @entity74 ) is a @entity395 caused by activating mutations of the @entity460 -sensing receptor ( @entity1631 ). The treatment of @entity74 @entity1 with 1a-hydroxylated @entity560 derivatives can cause @entity5200 leading to @entity11604 . DESIGN AND METHODS: We studied a @entity1 who presented with @entity261 and asymptomatic @entity3747 at age 2.5 years. Mutations of @entity1631 were investigated by DNA sequencing. Functional analyses of mutant and @entity7097 CASRs were done in transiently transfected @entity1 embryonic kidney (HEK293) cells. RESULTS: The proband and her father are heterozygous for an eight- @entity4334 deletion @entity69976 in the @entity1631 encoding the intracellular domain of the protein. Transient expression of @entity1631 constructs in kidney cells in vitro suggested greater cell surface expression of the mutant receptor with a left-shifted extracellular @entity460 dose-response curve relative to that of the @entity7097 receptor consistent with gain of function. Initial treatment of the @entity1 with @entity3873 led to increased urinary @entity460 excretion. Evaluation for mosaicism in the paternal grandparents of the proband was negative. CONCLUSIONS: We describe a novel naturally occurring deletion mutation within the @entity1631 that apparently arose de novo in the father of the @entity74 proband. Functional analysis suggests that the cytoplasmic tail of the @entity1631 contains determinants that regulate the attenuation of signal transduction. Early molecular analysis of the @entity1631 gene in @entity1 with isolated @entity261 is recommended because of its relevance to clinical outcome and treatment choice. In @entity74 @entity1 , @entity460 supplementation and low-dose @entity3875 avoids hypocalcemic symptoms without compromising renal function.

Novel @entity460 -sensing receptor cytoplasmic tail deletion mutation causing autosomal dominant XXXX : molecular and clinical study.

@entity1 :: ('9606', 'Species') :: ['girl', 'human', 'patients', 'patient'] @entity1631 :: ('846', 'Gene') :: ['CASR'] @entity3747 :: ('MESH:D006996', 'Disease') :: ['hypocalcemia'] @entity3875 :: ('MESH:D002762', 'Chemical') :: ['cholecalciferol'] @entity7097 :: ('MESH:C536751', 'Disease') :: ['WT'] @entity3873 :: ('MESH:D002117', 'Chemical') :: ['calcitriol'] @entity11604 :: ('MESH:D009397', 'Disease') :: ['nephrocalcinosis'] @entity261 :: ('MESH:D007011', 'Disease') :: ['idiopathic hypoparathyroidism', 'hypoparathyroidism'] @entity4334 :: ('D009711', 'Chemical') :: ['nucleotide'] @entity74 :: ('MESH:D030342', 'Disease') :: ['Autosomal dominant hypocalcemia', 'ADH'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity395 :: ('MESH:D035583', 'Disease') :: ['rare disorder'] @entity5200 :: ('MESH:D053565', 'Disease') :: ['hypercalciuria'] @entity69976 :: ('c|DEL|2703_2710|CCTTGGAG', 'DNAMutation') :: ['c.2703_2710delCCTTGGAG'] @entity560 :: ('MESH:D014807', 'Chemical') :: ['vitamin D']
@entity3747 :: (MESH:D006996,Disease) :: ['hypocalcemia']
