Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular Modeling
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-l...
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doaj-e2976b88cf5e4e80a013a27f5f823bb82020-11-25T01:24:52ZengHindawi LimitedCase Reports in Genetics2090-65442090-65522020-01-01202010.1155/2020/32565393256539Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular ModelingJohn E. Richter Jr.0Charitha Vadlamudi1Sarah K. Macklin2Ayesha Samreen3Haytham Helmi4Daniel Broderick5Ahmed N. Mohammad6Stephanie L. Hines7Jay A. VanGerpen8Paldeep S. Atwal9Thomas R. Caulfield10Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL 32224, USADepartment of Pulmonology, Mayo Clinic, Jacksonville, FL 32224, USADepartment of Clinical Genomics, Mayo Clinic, Jacksonville, FL 32224, USADepartment of Endocrinology, Mayo Clinic, Jacksonville, FL 32224, USADepartment of Clinical Genomics, Mayo Clinic, Jacksonville, FL 32224, USADepartment of Radiology, Mayo Clinic, Jacksonville, FL 32224, USADepartment of Clinical Genomics, Mayo Clinic, Jacksonville, FL 32224, USADepartment of Internal Medicine, Mayo Clinic, Jacksonville, FL 32224, USADepartment of Neurology, Mayo Clinic, Jacksonville, FL 32224, USADepartment of Clinical Genomics, Mayo Clinic, Jacksonville, FL 32224, USADepartment of Clinical Genomics, Mayo Clinic, Jacksonville, FL 32224, USABackground. 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 was analyzed using our protein informatics platform (PIP). Personalized protein-level molecular studies were completed on genetic testing data, complementing the analysis and clinical study. Results. A case of adult onset adrenomyeloneuropathy (AMN) and a novel ABCD1 variant are presented. The unique ABCD1 protein is discussed, and the proband’s case is compared to existing reports of AMN. 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.http://dx.doi.org/10.1155/2020/3256539 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
John E. Richter Jr. 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 |
spellingShingle |
John E. Richter Jr. 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 Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular Modeling Case Reports in Genetics |
author_facet |
John E. Richter Jr. 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 |
author_sort |
John E. Richter Jr. |
title |
Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular Modeling |
title_short |
Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular Modeling |
title_full |
Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular Modeling |
title_fullStr |
Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular Modeling |
title_full_unstemmed |
Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular Modeling |
title_sort |
characterization of a pathogenic variant in the abcd1 gene through protein molecular modeling |
publisher |
Hindawi Limited |
series |
Case Reports in Genetics |
issn |
2090-6544 2090-6552 |
publishDate |
2020-01-01 |
description |
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 was analyzed using our protein informatics platform (PIP). Personalized protein-level molecular studies were completed on genetic testing data, complementing the analysis and clinical study. Results. A case of adult onset adrenomyeloneuropathy (AMN) and a novel ABCD1 variant are presented. The unique ABCD1 protein is discussed, and the proband’s case is compared to existing reports of AMN. 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. |
url |
http://dx.doi.org/10.1155/2020/3256539 |
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