Matches in SemOpenAlex for { <https://semopenalex.org/work/W2145409831> ?p ?o ?g. }
Showing items 1 to 60 of
60
with 100 items per page.
- W2145409831 abstract "Rickets and osteomalacia, which result in softening of the bones from lack of vitamin D, can be caused by either dietary vitamin D deficiency or mutations in the vitamin D receptor. These maladies have largely been controlled by widespread use of calcium and vitamin D supplementation in public health. However, incidence of idiopathic infantile hypercalcemia—a rare pediatric autosomal recessive disorder characterized by too much calcium in the blood and kidneys, failure to thrive, vomiting, and dehydration—has increased in England during this period of high vitamin D supplementation. Now, in an elegant genomic study using a candidate-gene approach, Schlingmann et al. identify the molecular underpinning of this disease.Schlingmann et al. evaluated six infants from four families with idiopathic infantile hypercalcemia and used their peripheral blood cells to identify defective genes in the vitamin D metabolic pathway. They identified both homozygous and compound heterozygous mutations in the gene encoding the vitamin D–metabolizing enzyme CYP24A1 . Similar mutations were also identified in a second cohort of four children who developed severe hypercalcemia after a single high dose of oral vitamin D supplementation, which is presumably a milder version of idiopathic infantile hypercalcemia. Most importantly, the authors found that most of these mutations resulted in complete loss of CYP24A1 function when expressed in cell culture models and subsequently diminished or decreased metabolism of vitamin D products. The phenotypes of these mutations bear striking similarity to a mouse knockout model of CYP24A1 . Protein structural analysis indicated that these mutations probably affect critical regions of the protein that are important for its folding, enzymatic activity, or substrate binding, therefore resulting in loss of function.These results demonstrate a causative role of CYP24A1 in the molecular pathogenesis of idiopathic infantile hypercalcemia and add to the growing list of components of the vitamin D signaling pathway implicated in human diseases. These studies not only indicate caution for general prophylactic vitamin D administration, they also provide an attractive druggable enzymatic target for perhaps much larger populations of patients with vitamin D deficiency, such as the elderly.K. P. Schlingmann et al. , Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N. Engl. J. Med. 365 , 410–421 (2011). [[Abstract]][1] [1]: http://www.nejm.org/doi/full/10.1056/NEJMoa1103864" @default.
- W2145409831 created "2016-06-24" @default.
- W2145409831 creator A5023480510 @default.
- W2145409831 date "2011-08-17" @default.
- W2145409831 modified "2023-09-24" @default.
- W2145409831 title "Too Much of a Good Thing" @default.
- W2145409831 doi "https://doi.org/10.1126/scitranslmed.3003034" @default.
- W2145409831 hasPublicationYear "2011" @default.
- W2145409831 type Work @default.
- W2145409831 sameAs 2145409831 @default.
- W2145409831 citedByCount "0" @default.
- W2145409831 crossrefType "journal-article" @default.
- W2145409831 hasAuthorship W2145409831A5023480510 @default.
- W2145409831 hasConcept C124490489 @default.
- W2145409831 hasConcept C126322002 @default.
- W2145409831 hasConcept C134018914 @default.
- W2145409831 hasConcept C179639408 @default.
- W2145409831 hasConcept C2776489590 @default.
- W2145409831 hasConcept C2776917539 @default.
- W2145409831 hasConcept C2776940978 @default.
- W2145409831 hasConcept C2778049618 @default.
- W2145409831 hasConcept C71924100 @default.
- W2145409831 hasConcept C76743606 @default.
- W2145409831 hasConceptScore W2145409831C124490489 @default.
- W2145409831 hasConceptScore W2145409831C126322002 @default.
- W2145409831 hasConceptScore W2145409831C134018914 @default.
- W2145409831 hasConceptScore W2145409831C179639408 @default.
- W2145409831 hasConceptScore W2145409831C2776489590 @default.
- W2145409831 hasConceptScore W2145409831C2776917539 @default.
- W2145409831 hasConceptScore W2145409831C2776940978 @default.
- W2145409831 hasConceptScore W2145409831C2778049618 @default.
- W2145409831 hasConceptScore W2145409831C71924100 @default.
- W2145409831 hasConceptScore W2145409831C76743606 @default.
- W2145409831 hasLocation W21454098311 @default.
- W2145409831 hasOpenAccess W2145409831 @default.
- W2145409831 hasPrimaryLocation W21454098311 @default.
- W2145409831 hasRelatedWork W2057143724 @default.
- W2145409831 hasRelatedWork W2071150043 @default.
- W2145409831 hasRelatedWork W2088172789 @default.
- W2145409831 hasRelatedWork W2110714814 @default.
- W2145409831 hasRelatedWork W2173526219 @default.
- W2145409831 hasRelatedWork W2185826627 @default.
- W2145409831 hasRelatedWork W2209323210 @default.
- W2145409831 hasRelatedWork W2275237436 @default.
- W2145409831 hasRelatedWork W2315648199 @default.
- W2145409831 hasRelatedWork W2415760735 @default.
- W2145409831 hasRelatedWork W2442706368 @default.
- W2145409831 hasRelatedWork W2752294535 @default.
- W2145409831 hasRelatedWork W2808780484 @default.
- W2145409831 hasRelatedWork W2892011026 @default.
- W2145409831 hasRelatedWork W2907401918 @default.
- W2145409831 hasRelatedWork W2922203460 @default.
- W2145409831 hasRelatedWork W2941011769 @default.
- W2145409831 hasRelatedWork W3022264712 @default.
- W2145409831 hasRelatedWork W3113450445 @default.
- W2145409831 hasRelatedWork W2964922509 @default.
- W2145409831 isParatext "false" @default.
- W2145409831 isRetracted "false" @default.
- W2145409831 magId "2145409831" @default.
- W2145409831 workType "article" @default.