John E Richter, Charitha Vadlamudi, Sarah K Macklin, Ayesha Samreen, Haytham Helmi, Daniel Broderick, Ahmed N Mohammad, Stephanie L Hines, Jay A VanGerpen, Paldeep S Atwal, Thomas R Caulfield
{"title":"Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular Modeling.","authors":"John E Richter, Charitha Vadlamudi, Sarah K Macklin, Ayesha Samreen, Haytham Helmi, Daniel Broderick, Ahmed N Mohammad, Stephanie L Hines, Jay A VanGerpen, Paldeep S Atwal, Thomas R Caulfield","doi":"10.1155/2020/3256539","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The ATP-binding cassette, subfamily D, member 1 (ABCD1) protein is a peroxisomal half-transporter that allows for very long chain fatty acid (VLCFA) degradation. Pathogenic variants of <i>ABCD1</i> cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death.</p><p><strong>Methods: </strong>A newly characterized and suspected pathogenic variant in <i>ABCD1</i> cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death.</p><p><strong>Results: </strong>A case of adult onset adrenomyeloneuropathy (AMN) and a novel <i>ABCD1</i> cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death.</p><p><strong>Conclusions: </strong>Data fusion from multiple sources was combined in a comprehensive approach yielding an enriched assessment of the patient's disease and prognosis. Molecular modeling was performed on the variant to better characterize its clinical significance and confirm pathogenicity.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/3256539","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Case Reports in Genetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2020/3256539","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 2
Abstract
Background: The ATP-binding cassette, subfamily D, member 1 (ABCD1) protein is a peroxisomal half-transporter that allows for very long chain fatty acid (VLCFA) degradation. Pathogenic variants of ABCD1 cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death.
Methods: A newly characterized and suspected pathogenic variant in ABCD1 cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death.
Results: A case of adult onset adrenomyeloneuropathy (AMN) and a novel ABCD1 cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death.
Conclusions: Data fusion from multiple sources was combined in a comprehensive approach yielding an enriched assessment of the patient's disease and prognosis. Molecular modeling was performed on the variant to better characterize its clinical significance and confirm pathogenicity.
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