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dc.contributor.authorRichmond, Christopher M
dc.contributor.authorCampbell, Sally
dc.contributor.authorFoo, Hee W
dc.contributor.authorLunke, Sebastian
dc.contributor.authorStark, Zornitza
dc.contributor.authorMoody, Amanda
dc.contributor.authorBannister, Elizabeth
dc.contributor.authorGreenway, Anthea
dc.contributor.authorBrown, Natasha
dc.date.accessioned2020-08-05T05:53:42Z
dc.date.available2020-08-05T05:53:42Z
dc.date.issued2020
dc.identifier.issn1661-8769
dc.identifier.doi10.1159/000505886
dc.identifier.urihttp://hdl.handle.net/10072/396222
dc.description.abstractHeterozygous pathogenic variants in SPTB cause autosomal dominant hereditary spherocytosis, an important cause of neonatal nonimmune hemolytic anemia. Biallelic mutations are rarely reported, all with severe neonatal presentation. We describe rapid (68 h) genomic diagnosis of homozygous β-spectrin deficiency in a newborn with severe transfusion-dependent hemolytic anemia, conjugated hyperbilirubinemia, and progressive liver failure. Trio whole-exome sequencing identified a novel biallelic SPTB variant (c.6119C>T; p.Thr2040Ile) located in the critical spectrin repeat region. Pretransfusion blood film showed marked spherocytosis including microspherocytes and nucleated erythrocytes, and eosin-5-maleimide (E5M) staining was markedly reduced, supporting pathogenicity. Both asymptomatic heterozygous parents demonstrated mildly reduced E5M staining, with occasional spherocytes and elliptocytes. Early molecular diagnosis facilitated hypertransfusion to suppress ineffective erythropoiesis and reverse hepatic dysfunction. This report broadens the genotypic and phenotypic spectrum of spectrin deficiency and highlights the utility of rapid genomic testing in facilitating early diagnosis and informing targeted therapy in critically ill patients.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherKarger
dc.relation.ispartofpagefrom50
dc.relation.ispartofpageto55
dc.relation.ispartofissue1
dc.relation.ispartofjournalMolecular Syndromology
dc.relation.ispartofvolume11
dc.subject.fieldofresearchGenetics
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchcode3105
dc.subject.fieldofresearchcode3202
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsMedical genomics
dc.subject.keywordsRapid exome sequencing
dc.subject.keywordsHeredity
dc.titleRapid Identification of Biallelic SPTB Mutation in a Neonate with Severe Congenital Hemolytic Anemia and Liver Failure
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationRichmond, CM; Campbell, S; Foo, HW; Lunke, S; Stark, Z; Moody, A; Bannister, E; Greenway, A; Brown, N, Rapid Identification of Biallelic SPTB Mutation in a Neonate with Severe Congenital Hemolytic Anemia and Liver Failure, Molecular Syndromology, 2020, 11 (1), pp. 50-55
dcterms.dateAccepted2019-12-05
dc.date.updated2020-08-05T05:52:03Z
gro.hasfulltextNo Full Text
gro.griffith.authorRichmond, Chris M.


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