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dc.contributor.authorShepard, PJ
dc.contributor.authorBarshop, BA
dc.contributor.authorBaumgartner, MR
dc.contributor.authorJepsen, K
dc.contributor.authorHansen, John-Bjarne
dc.contributor.authorSmith, EN
dc.contributor.authorFrazer, Kelly
dc.date.accessioned2022-05-18T12:13:54Z
dc.date.available2022-05-18T12:13:54Z
dc.date.issued2014-11-06
dc.description.abstractPurpose: 3-Methylcrotonyl-CoA carboxylase deficiency (MCCD) is an autosomal recessive disorder of leucine catabolism that has a highly variable clinical phenotype, ranging from acute metabolic acidosis to nonspecific symptoms such as developmental delay, failure to thrive, hemiparesis, muscular hypotonia, and multiple sclerosis. Implementation of newborn screening for MCCD has resulted in broadening the range of phenotypic expression to include asymptomatic adults. The purpose of this study was to identify factors underlying the varying phenotypes of MCCD.<p> <p>Methods: We performed exome sequencing on DNA from 33 cases and 108 healthy controls. We examined these data for associations between either MCC mutational status, genetic ancestry, or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases. <p>Results: We determined that individuals with nonspecific clinical phenotypes are highly inbred compared with cases that are asymptomatic and healthy controls. For 5 of these 10 individuals, we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their nonspecific clinical phenotypes previously attributed to MCCD. <p>Conclusion: Our study shows that nonspecific phenotypes attributed to MCCD are associated with consanguinity and are likely not due to mutations in the MCC enzyme but result from rare homozygous mutations in other disease genes.en_US
dc.identifier.citationShepard, Barshop, Baumgartner, Jepsen, Hansen JB, Smith E, Frazer K. Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD. Genetics in Medicine. 2015;17(8):660-667en_US
dc.identifier.cristinIDFRIDAID 1193824
dc.identifier.doi10.1038/gim.2014.157
dc.identifier.issn1098-3600
dc.identifier.issn1530-0366
dc.identifier.urihttps://hdl.handle.net/10037/25172
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalGenetics in Medicine
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2015 The Author(s)en_US
dc.titleConsanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCDen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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