FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387358260> ?p ?o ?g. }

• W4387358260 abstract "Abstract Disclosure: D.S. Ali: None. F. Marini: None. F. Alsarraf: None. H.H. Alalwani: None. A. Alamri: None. A.A. Khan: Advisory Board Member; Self; Amgen Inc, Takeda. Grant Recipient; Self; Amgen Inc, Alexion Pharmaceuticals, Inc., Takeda, Ultragenyx, Radius Health, Inc. M. Brandi: Consulting Fee; Self; Alexion Pharmaceuticals, Inc. Speaker; Self; Amgen Inc, Alexion Pharmaceuticals, Inc., Eli Lilly & Company. Background: Autosomal dominant hypocalcemia (ADH1) is a genetic disorder characterized by low serum calcium and low or inappropriately normal parathyroid hormone levels. It is caused by a heterozygous activating mutation of the calcium-sensing receptor (CaSR) gene. ADH1 has been linked to 113 unique germline mutations, of which 96% are missense mutations. There is a lack of clear genotype-phenotype correlation in the reported literature. Methods: We described a case series of six unrelated ADH1 probands, each with a gain-of-function CaSR mutation, and two children of one of these cases, comparing clinical, biochemical, and complication profiles and matching our identified mutations to those previously reported in the literature. Results: Of our cases 75% are familial and 25% are secondary to de novo mutation. Our 6 unrelated ADH1 probands showed distinct clinical presentations, while 3 cases within the same pedigree shared similar presentation and clinical characteristics including presentation in infancy, hypocalcemic seizures (2/3; 66.7%), hypomagnesemia, hyperphosphatemia, and hypercalciuria. The biochemical profile differed among the 6 cases in the degree of hypocalcemia, associated hypercalciuria, hypomagnesemia, and/or hypokalemia. Response to therapy also differed. When comparing our cases to previously published cases, we noted that mutations in the 5th transmembrane domain of the CaSR (TM5) carry a more severe form of the disease and may be associated with a higher rate of hypocalcemic seizures, basal ganglia calcifications as well as nephrocalcinosis, nephrolithiasis and renal insufficiency compared to mutations in the extracellular regions. Hypomagnesemia was present in 100% of the cases harboring mutations in TM5. We also describe two novel activating mutations of the CaSR gene; c.2468T&gt;A, p.lle823Asn and c.1756G&gt;A, p.Glu586Lys. Both of these were not reported either on the most common databases of human mutations or in the literature. In silico analysis of p.lle823Asn by PolyPhen-2 predicted the Ile to Asn substitution at position 823 as “probably damaging”, while the p.Glu586Lys substitution was suggested to have a “benign” nature. Our patient with the former mutation had a history of seizure and nephrolithiasis, while our patient with the latter mutation is mildly symptomatic, presented in her 40s, and is on low doses of active vitamin D and calcium supplements. Conclusion: As a result of these genetic and clinical comparisons, we propose that a genotype-phenotype correlation may exist because our cases showed similar presentation, characteristics, and severity, with respect to published cases with the same or similar mutations. We also contended that the severity of the presentation is highly influenced by the specific CaSR variant. These findings, however, require further evaluation and assessment with a systematic review. Presentation: Saturday, June 17, 2023" @default.
• W4387358260 created "2023-10-06" @default.
• W4387358260 creator A5031618531 @default.
• W4387358260 creator A5034789006 @default.
• W4387358260 creator A5053396414 @default.
• W4387358260 creator A5055069129 @default.
• W4387358260 creator A5061165605 @default.
• W4387358260 creator A5062890723 @default.
• W4387358260 creator A5063080270 @default.
• W4387358260 date "2023-10-01" @default.
• W4387358260 modified "2023-10-16" @default.
• W4387358260 title "OR23-02 Genotype-Phenotype Correlation In Calcium Sensing Receptor (Casr) Gene Gain-Of-Function Mutations: A Case Series And Report Of 2 Novel Mutations" @default.
• W4387358260 doi "https://doi.org/10.1210/jendso/bvad114.560" @default.
• W4387358260 hasPublicationYear "2023" @default.
• W4387358260 type Work @default.
• W4387358260 citedByCount "0" @default.
• W4387358260 crossrefType "journal-article" @default.
• W4387358260 hasAuthorship W4387358260A5031618531 @default.
• W4387358260 hasAuthorship W4387358260A5034789006 @default.
• W4387358260 hasAuthorship W4387358260A5053396414 @default.
• W4387358260 hasAuthorship W4387358260A5055069129 @default.
• W4387358260 hasAuthorship W4387358260A5061165605 @default.
• W4387358260 hasAuthorship W4387358260A5062890723 @default.
• W4387358260 hasAuthorship W4387358260A5063080270 @default.
• W4387358260 hasBestOaLocation W43873582601 @default.
• W4387358260 hasConcept C104317684 @default.
• W4387358260 hasConcept C126322002 @default.
• W4387358260 hasConcept C142590548 @default.
• W4387358260 hasConcept C178790620 @default.
• W4387358260 hasConcept C185592680 @default.
• W4387358260 hasConcept C187212893 @default.
• W4387358260 hasConcept C188997412 @default.
• W4387358260 hasConcept C2776183862 @default.
• W4387358260 hasConcept C2777724520 @default.
• W4387358260 hasConcept C501734568 @default.
• W4387358260 hasConcept C519063684 @default.
• W4387358260 hasConcept C543218039 @default.
• W4387358260 hasConcept C54355233 @default.
• W4387358260 hasConcept C71924100 @default.
• W4387358260 hasConcept C75563809 @default.
• W4387358260 hasConcept C86803240 @default.
• W4387358260 hasConcept C87975464 @default.
• W4387358260 hasConceptScore W4387358260C104317684 @default.
• W4387358260 hasConceptScore W4387358260C126322002 @default.
• W4387358260 hasConceptScore W4387358260C142590548 @default.
• W4387358260 hasConceptScore W4387358260C178790620 @default.
• W4387358260 hasConceptScore W4387358260C185592680 @default.
• W4387358260 hasConceptScore W4387358260C187212893 @default.
• W4387358260 hasConceptScore W4387358260C188997412 @default.
• W4387358260 hasConceptScore W4387358260C2776183862 @default.
• W4387358260 hasConceptScore W4387358260C2777724520 @default.
• W4387358260 hasConceptScore W4387358260C501734568 @default.
• W4387358260 hasConceptScore W4387358260C519063684 @default.
• W4387358260 hasConceptScore W4387358260C543218039 @default.
• W4387358260 hasConceptScore W4387358260C54355233 @default.
• W4387358260 hasConceptScore W4387358260C71924100 @default.
• W4387358260 hasConceptScore W4387358260C75563809 @default.
• W4387358260 hasConceptScore W4387358260C86803240 @default.
• W4387358260 hasConceptScore W4387358260C87975464 @default.
• W4387358260 hasIssue "Supplement_1" @default.
• W4387358260 hasLocation W43873582601 @default.
• W4387358260 hasOpenAccess W4387358260 @default.
• W4387358260 hasPrimaryLocation W43873582601 @default.
• W4387358260 hasRelatedWork W1966771777 @default.
• W4387358260 hasRelatedWork W1989089727 @default.
• W4387358260 hasRelatedWork W2097771334 @default.
• W4387358260 hasRelatedWork W2326119275 @default.
• W4387358260 hasRelatedWork W2375386393 @default.
• W4387358260 hasRelatedWork W2400085847 @default.
• W4387358260 hasRelatedWork W3173734647 @default.
• W4387358260 hasRelatedWork W3203595062 @default.
• W4387358260 hasRelatedWork W4254695004 @default.
• W4387358260 hasRelatedWork W4255038994 @default.
• W4387358260 hasVolume "7" @default.
• W4387358260 isParatext "false" @default.
• W4387358260 isRetracted "false" @default.
• W4387358260 workType "article" @default.