Matches in SemOpenAlex for { <https://semopenalex.org/work/W4210289288> ?p ?o ?g. }
Showing items 1 to 89 of
89
with 100 items per page.
- W4210289288 endingPage "mcs.a006165" @default.
- W4210289288 startingPage "mcs.a006165" @default.
- W4210289288 abstract "Noncoding and synonymous coding variants that exert their effects via alternative splicing are increasingly recognized as an important category of disease-causing variants. In this report, we describe two siblings who presented with hypotonia, profound developmental delays, and seizures. Brain magnetic resonance imaging (MRI) in the proband at 5 yr showed diffuse cerebral and cerebellar white matter volume loss. Both siblings later developed ventilator-dependent respiratory insufficiency and scoliosis and are currently nonverbal and nonambulatory. Extensive molecular testing including oligo array and clinical exome sequencing was nondiagnostic. Research genome sequencing under an institutional review board (IRB)-approved study protocol revealed that both affected children were compound-heterozygous for variants in the SEPSECS gene. One variant was an initiator codon change (c.1A > T) that disrupted protein translation, consistent with the observation that most disease-causing variants are loss-of-function changes. The other variant was a coding change (c.846G > A) that was predicted to be synonymous but had been demonstrated to disrupt mRNA splicing in a minigene assay. The SEPSECS gene encodes O-phosphoseryl-tRNA(Sec) selenium transferase, an enzyme that participates in the biosynthesis and transport of selenoproteins in the body. Variations in SEPSECS cause autosomal recessive pontocerebellar hypoplasia type 2D (PCHT 2D; OMIM #613811), a neurodegenerative condition characterized by progressive cerebrocerebellar atrophy, microcephaly, and epileptic encephalopathy. The identification of biallelic pathogenic variants in this family-one of which was a synonymous change not identified by prior clinical testing-not only ended the diagnostic odyssey for this family but also highlights the contribution of occult pathogenic variants that may not be recognized by standard genetic testing methodologies." @default.
- W4210289288 created "2022-02-08" @default.
- W4210289288 creator A5004760628 @default.
- W4210289288 creator A5012975065 @default.
- W4210289288 creator A5014714324 @default.
- W4210289288 creator A5022808238 @default.
- W4210289288 creator A5023379825 @default.
- W4210289288 creator A5035655600 @default.
- W4210289288 creator A5043123384 @default.
- W4210289288 creator A5047502918 @default.
- W4210289288 creator A5058229103 @default.
- W4210289288 creator A5065840657 @default.
- W4210289288 creator A5080770864 @default.
- W4210289288 creator A5090966761 @default.
- W4210289288 date "2022-01-28" @default.
- W4210289288 modified "2023-10-18" @default.
- W4210289288 title "Biallelic SEPSECS variants in two siblings with pontocerebellar hypoplasia type 2D underscore the relevance of splice-disrupting synonymous variants in disease." @default.
- W4210289288 cites W1507819731 @default.
- W4210289288 cites W2046421695 @default.
- W4210289288 cites W2054380003 @default.
- W4210289288 cites W2106578986 @default.
- W4210289288 cites W2126148683 @default.
- W4210289288 cites W2126799109 @default.
- W4210289288 cites W2131187246 @default.
- W4210289288 cites W2133202433 @default.
- W4210289288 cites W2158228504 @default.
- W4210289288 cites W2782289439 @default.
- W4210289288 cites W2799812275 @default.
- W4210289288 cites W2808706850 @default.
- W4210289288 cites W2979935292 @default.
- W4210289288 doi "https://doi.org/10.1101/mcs.a006165" @default.
- W4210289288 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35091508" @default.
- W4210289288 hasPublicationYear "2022" @default.
- W4210289288 type Work @default.
- W4210289288 citedByCount "0" @default.
- W4210289288 crossrefType "journal-article" @default.
- W4210289288 hasAuthorship W4210289288A5004760628 @default.
- W4210289288 hasAuthorship W4210289288A5012975065 @default.
- W4210289288 hasAuthorship W4210289288A5014714324 @default.
- W4210289288 hasAuthorship W4210289288A5022808238 @default.
- W4210289288 hasAuthorship W4210289288A5023379825 @default.
- W4210289288 hasAuthorship W4210289288A5035655600 @default.
- W4210289288 hasAuthorship W4210289288A5043123384 @default.
- W4210289288 hasAuthorship W4210289288A5047502918 @default.
- W4210289288 hasAuthorship W4210289288A5058229103 @default.
- W4210289288 hasAuthorship W4210289288A5065840657 @default.
- W4210289288 hasAuthorship W4210289288A5080770864 @default.
- W4210289288 hasAuthorship W4210289288A5090966761 @default.
- W4210289288 hasBestOaLocation W42102892881 @default.
- W4210289288 hasConcept C104317684 @default.
- W4210289288 hasConcept C120821319 @default.
- W4210289288 hasConcept C12125453 @default.
- W4210289288 hasConcept C141231307 @default.
- W4210289288 hasConcept C16671776 @default.
- W4210289288 hasConcept C188997412 @default.
- W4210289288 hasConcept C2779546488 @default.
- W4210289288 hasConcept C501734568 @default.
- W4210289288 hasConcept C54355233 @default.
- W4210289288 hasConcept C86803240 @default.
- W4210289288 hasConceptScore W4210289288C104317684 @default.
- W4210289288 hasConceptScore W4210289288C120821319 @default.
- W4210289288 hasConceptScore W4210289288C12125453 @default.
- W4210289288 hasConceptScore W4210289288C141231307 @default.
- W4210289288 hasConceptScore W4210289288C16671776 @default.
- W4210289288 hasConceptScore W4210289288C188997412 @default.
- W4210289288 hasConceptScore W4210289288C2779546488 @default.
- W4210289288 hasConceptScore W4210289288C501734568 @default.
- W4210289288 hasConceptScore W4210289288C54355233 @default.
- W4210289288 hasConceptScore W4210289288C86803240 @default.
- W4210289288 hasLocation W42102892881 @default.
- W4210289288 hasLocation W42102892882 @default.
- W4210289288 hasLocation W42102892883 @default.
- W4210289288 hasOpenAccess W4210289288 @default.
- W4210289288 hasPrimaryLocation W42102892881 @default.
- W4210289288 hasRelatedWork W2287693578 @default.
- W4210289288 hasRelatedWork W2610593425 @default.
- W4210289288 hasRelatedWork W2625779927 @default.
- W4210289288 hasRelatedWork W3001328357 @default.
- W4210289288 hasRelatedWork W3038471052 @default.
- W4210289288 hasRelatedWork W3141049175 @default.
- W4210289288 hasRelatedWork W3209450440 @default.
- W4210289288 hasRelatedWork W4310157916 @default.
- W4210289288 hasRelatedWork W4362733549 @default.
- W4210289288 hasRelatedWork W4386272282 @default.
- W4210289288 isParatext "false" @default.
- W4210289288 isRetracted "false" @default.
- W4210289288 workType "article" @default.