A Novel Missense Variant of the ABCD1 Gene in X‐Linked Adrenoleukodystrophy in Chinese Family
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| Publicado en: | Molecular Genetics & Genomic Medicine vol. 13, no. 10 (Oct 1, 2025) |
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| Otros Autores: | , , , , |
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John Wiley & Sons, Inc.
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| Acceso en línea: | Citation/Abstract Full Text Full Text - PDF |
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| 003 | UK-CbPIL | ||
| 022 | |a 2324-9269 | ||
| 024 | 7 | |a 10.1002/mgg3.70148 |2 doi | |
| 035 | |a 3264787835 | ||
| 045 | 0 | |b d20251001 | |
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| 100 | 1 | |a Fu, Hongxia |u Department of Neurology, SSL, Central Hospital of Dongguan City, Affiliated Dongguan Shilong People's Hospital of Guangdong Medical University, Dongguan, China | |
| 245 | 1 | |a A Novel Missense Variant of the ABCD1 Gene in X‐Linked Adrenoleukodystrophy in Chinese Family | |
| 260 | |b John Wiley & Sons, Inc. |c Oct 1, 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a ABSTRACT Background We identified a novel ABCD1 variant (c.773T>G, p.Leu258Arg, NM_000033.4) in a Chinese pedigree affected by X‐linked adrenoleukodystrophy (X‐ALD). This missense variant in exon 1 is predicted to be pathogenic and likely constitutes the genetic basis of the disease phenotype in this family. Methods ABCD1 gene sequencing was performed in the Chinese pedigree. The pathogenicity of identified variants was assessed using computational prediction tools. Subcellular localization studies were conducted, and very‐long‐chain fatty acid (VLCFA) levels were quantified in patient‐derived samples. Results Sequencing analysis identified a hemizygous missense variant in the ABCD1 gene (c.773T>G; p.Leu258Arg). In silico pathogenicity prediction using SIFT and PolyPhen‐2 algorithms classified the p.Leu258Arg substitution as deleterious. Functional characterization revealed that the p.Leu258Arg variant impairs the peroxisomal membrane localization of the ABCD1 protein. Consistent with the established role of ABCD1 in peroxisomal β‐oxidation, individuals harboring this variant exhibited significantly elevated serum levels of VLCFA. Specifically, the C26:0/C22:0 ratio was elevated 2.8‐fold compared to control values, confirming impaired VLCFA metabolism. Conclusion In accordance with the “Standards and Guidelines for the Interpretation of Sequence Variants” established by the American College of Medical Genetics and Genomics (ACMG), we assessed the pathogenicity of the novel ABCD1 gene variant c.773T>G. This variant meets the following ACMG evidence criteria: PM1 (located within a critical functional domain or mutational hotspot known to lack benign variation); PM2 (absent or observed at very low frequency in population databases e.g., gnomAD, EXAC, 1000 Genomes); PP3 (multiple in silico prediction tools consistently suggest a deleterious effect on the gene or gene product). Integrating this evidence (PM1 + PM2 + PP3), the variant is classified as likely pathogenic based on ACMG guidelines. Experimental data from this study further substantiate the pathogenicity of the c.773T>G variant located in exon 1 of the ABCD1 gene. This finding broadens the spectrum of known pathogenic mutations in ABCD1 associated with X‐ALD and provides crucial information for the molecular diagnosis of affected patients. | |
| 651 | 4 | |a United States--US | |
| 653 | |a Guidelines | ||
| 653 | |a Sequence analysis | ||
| 653 | |a Hypothesis testing | ||
| 653 | |a Memory | ||
| 653 | |a Mutation | ||
| 653 | |a Pathogenicity | ||
| 653 | |a Phenotypes | ||
| 653 | |a Genetic counseling | ||
| 653 | |a Oxidation | ||
| 653 | |a Localization | ||
| 653 | |a Ethics | ||
| 653 | |a Proteins | ||
| 653 | |a Pathogens | ||
| 653 | |a Hormone replacement therapy | ||
| 653 | |a Encephalitis | ||
| 653 | |a Mutation hot spots | ||
| 653 | |a Serum levels | ||
| 653 | |a Predictions | ||
| 653 | |a Gene sequencing | ||
| 653 | |a Autoimmune diseases | ||
| 653 | |a Magnetic resonance imaging | ||
| 653 | |a Genetics | ||
| 653 | |a Adrenoleukodystrophy | ||
| 653 | |a Pedigree | ||
| 653 | |a Very Low Frequencies | ||
| 653 | |a Software | ||
| 653 | |a Social | ||
| 700 | 1 | |a Han, Lu |u Department of Central Laboratory, SSL, Central Hospital of Dongguan City, Affiliated Dongguan Shilong People's Hospital of Guangdong Medical University, Dongguan, China | |
| 700 | 1 | |a Liu, Xianhong |u The Center for Precision Medicine, SSL, Central Hospital of Dongguan City, Affiliated Dongguan Shilong People's Hospital of Guangdong Medical University, Dongguan, China | |
| 700 | 1 | |a He, Bin |u Department of Central Laboratory, SSL, Central Hospital of Dongguan City, Affiliated Dongguan Shilong People's Hospital of Guangdong Medical University, Dongguan, China | |
| 700 | 1 | |a He, Pei |u Department of Obstetrics and Gynaecology, The Center for Reproductive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China | |
| 700 | 1 | |a Hu, Junjian |u Department of Central Laboratory, SSL, Central Hospital of Dongguan City, Affiliated Dongguan Shilong People's Hospital of Guangdong Medical University, Dongguan, China | |
| 773 | 0 | |t Molecular Genetics & Genomic Medicine |g vol. 13, no. 10 (Oct 1, 2025) | |
| 786 | 0 | |d ProQuest |t Biological Science Database | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3264787835/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text |u https://www.proquest.com/docview/3264787835/fulltext/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3264787835/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |