FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2891846704> ?p ?o ?g. }

• W2891846704 abstract "Context: The cholesterol side chain cleavage enzyme (CYP11A1) catalyzes the conversion of cholesterol to pregnenolone, the first rate-limiting step of steroidogenesis. CYP11A1 mutations are associated with primary adrenal insufficiency (PAI) as well as disorders of sex development (DSD) in 46,XY patients. Objective: To define the pathogenicity mechanism for the p.Glu314Lys variant, previously reported, and found in four additional patients with CYP11A1 deficiency. Subjects and Methods: DNA of four patients presenting with delayed PAI and/or 46,XY DSD were studied by Sanger or Massively Parallel sequencing. Three CYP11A1 mutations were characterized in vitro and in silico, and one by mRNA analysis on testicular tissue. Results: All patients were compound heterozygous for the previously described p.Glu314Lys variant. In silico studies predicted this mutation as benign with no effect on splicing but mRNA analysis found that it led to incomplete exon 5 skipping. This mechanism was confirmed by minigene experiment. The protein carrying this mutation without exon skipping should conserve almost normal activity, according to in vitro studies. Two other mutations found in trans, the p.Arg120Gln and p.Arg465Trp, had similar activity compared to negative control, consistent with the in silico studies. Conclusions: We provide biological proof that the p.Glu314Lys variant is pathogenic due to its impact on splicing and seems responsible for the moderate phenotype of the four patients reported herein. The present study highlights the importance of considering the potential effect of a missense variant on splicing when it is not predicted to be disease causing." @default.
• W2891846704 created "2018-09-27" @default.
• W2891846704 creator A5017806433 @default.
• W2891846704 creator A5029441085 @default.
• W2891846704 creator A5030732553 @default.
• W2891846704 creator A5031981590 @default.
• W2891846704 creator A5042736004 @default.
• W2891846704 creator A5050989671 @default.
• W2891846704 creator A5057431979 @default.
• W2891846704 creator A5064064148 @default.
• W2891846704 creator A5069718781 @default.
• W2891846704 creator A5078500914 @default.
• W2891846704 creator A5089791927 @default.
• W2891846704 date "2018-09-05" @default.
• W2891846704 modified "2023-10-13" @default.
• W2891846704 title "Aberrant Splicing Is the Pathogenicity Mechanism of the p.Glu314Lys Variant in CYP11A1 Gene" @default.
• W2891846704 cites W1797304158 @default.
• W2891846704 cites W1988874431 @default.
• W2891846704 cites W1991645074 @default.
• W2891846704 cites W2029142094 @default.
• W2891846704 cites W2039490460 @default.
• W2891846704 cites W2042178683 @default.
• W2891846704 cites W2051890768 @default.
• W2891846704 cites W2051978340 @default.
• W2891846704 cites W2076994020 @default.
• W2891846704 cites W2087390151 @default.
• W2891846704 cites W2093829435 @default.
• W2891846704 cites W2094557907 @default.
• W2891846704 cites W2099492603 @default.
• W2891846704 cites W2111966748 @default.
• W2891846704 cites W2116026368 @default.
• W2891846704 cites W2122589787 @default.
• W2891846704 cites W2125179627 @default.
• W2891846704 cites W2144201740 @default.
• W2891846704 cites W2159760570 @default.
• W2891846704 cites W2164259147 @default.
• W2891846704 cites W2167914935 @default.
• W2891846704 cites W2298595356 @default.
• W2891846704 cites W2309331091 @default.
• W2891846704 cites W2334043286 @default.
• W2891846704 cites W2344359206 @default.
• W2891846704 cites W2527725876 @default.
• W2891846704 cites W2736954792 @default.
• W2891846704 cites W2787741197 @default.
• W2891846704 doi "https://doi.org/10.3389/fendo.2018.00491" @default.
• W2891846704 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6134065" @default.
• W2891846704 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30233493" @default.
• W2891846704 hasPublicationYear "2018" @default.
• W2891846704 type Work @default.
• W2891846704 sameAs 2891846704 @default.
• W2891846704 citedByCount "19" @default.
• W2891846704 countsByYear W28918467042018 @default.
• W2891846704 countsByYear W28918467042019 @default.
• W2891846704 countsByYear W28918467042020 @default.
• W2891846704 countsByYear W28918467042021 @default.
• W2891846704 countsByYear W28918467042022 @default.
• W2891846704 countsByYear W28918467042023 @default.
• W2891846704 crossrefType "journal-article" @default.
• W2891846704 hasAuthorship W2891846704A5017806433 @default.
• W2891846704 hasAuthorship W2891846704A5029441085 @default.
• W2891846704 hasAuthorship W2891846704A5030732553 @default.
• W2891846704 hasAuthorship W2891846704A5031981590 @default.
• W2891846704 hasAuthorship W2891846704A5042736004 @default.
• W2891846704 hasAuthorship W2891846704A5050989671 @default.
• W2891846704 hasAuthorship W2891846704A5057431979 @default.
• W2891846704 hasAuthorship W2891846704A5064064148 @default.
• W2891846704 hasAuthorship W2891846704A5069718781 @default.
• W2891846704 hasAuthorship W2891846704A5078500914 @default.
• W2891846704 hasAuthorship W2891846704A5089791927 @default.
• W2891846704 hasBestOaLocation W28918467041 @default.
• W2891846704 hasConcept C104317684 @default.
• W2891846704 hasConcept C105580179 @default.
• W2891846704 hasConcept C151730666 @default.
• W2891846704 hasConcept C166342232 @default.
• W2891846704 hasConcept C194583182 @default.
• W2891846704 hasConcept C2775905019 @default.
• W2891846704 hasConcept C2778776201 @default.
• W2891846704 hasConcept C2779343474 @default.
• W2891846704 hasConcept C36823959 @default.
• W2891846704 hasConcept C501734568 @default.
• W2891846704 hasConcept C54355233 @default.
• W2891846704 hasConcept C54458228 @default.
• W2891846704 hasConcept C67705224 @default.
• W2891846704 hasConcept C75563809 @default.
• W2891846704 hasConcept C76818968 @default.
• W2891846704 hasConcept C80446465 @default.
• W2891846704 hasConcept C86803240 @default.
• W2891846704 hasConceptScore W2891846704C104317684 @default.
• W2891846704 hasConceptScore W2891846704C105580179 @default.
• W2891846704 hasConceptScore W2891846704C151730666 @default.
• W2891846704 hasConceptScore W2891846704C166342232 @default.
• W2891846704 hasConceptScore W2891846704C194583182 @default.
• W2891846704 hasConceptScore W2891846704C2775905019 @default.
• W2891846704 hasConceptScore W2891846704C2778776201 @default.
• W2891846704 hasConceptScore W2891846704C2779343474 @default.
• W2891846704 hasConceptScore W2891846704C36823959 @default.
• W2891846704 hasConceptScore W2891846704C501734568 @default.
• W2891846704 hasConceptScore W2891846704C54355233 @default.
• W2891846704 hasConceptScore W2891846704C54458228 @default.
• W2891846704 hasConceptScore W2891846704C67705224 @default.

• next