ArticleOrphanet journal of rare diseases2012
Preferential expression of mutant ABCD1 allele is common in adrenoleukodystrophy female carriers but unrelated to clinical symptoms.
Article in Orphanet journal of rare diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- X-linked competition - implications for human development and disease.Nature reviews. Genetics · 2025Review
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- Lipidomic biomarkers in plasma correlate with disease severity in adrenoleukodystrophy.Communications medicine · 2024Article
- Pathophysiology of X-Linked Adrenoleukodystrophy: Updates on Molecular Mechanisms.Journal of biotechnology and biomedicine · 2024Article
- Pitfalls of whole exome sequencing in undefined clinical conditions with a suspected genetic etiology.Genes & genomics · 2023Article
- X-linked adrenoleukodystrophy caused by maternal ABCD1 mutation and paternal X chromosome inactivation.Experimental and therapeutic medicine · 2022Article
- Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis.Genes · 2022Article
- The Impact of X-Chromosome Inactivation on Phenotypic Expression of X-Linked Neurodevelopmental Disorders.Brain sciences · 2021Review
- Clinical and Molecular Diagnosis of Beckwith-Wiedemann Syndrome with Single- or Multi-Locus Imprinting Disturbance.International journal of molecular sciences · 2021Review
- (Epi)genetic profiling of extraembryonic and postnatal tissues from female monozygotic twins discordant for Beckwith-Wiedemann syndrome.Molecular genetics & genomic medicine · 2020Article
- NovelEndocrinology and metabolism (Seoul, Korea) · 2020Article
- Skewed X-inactivation is common in the general female population.European journal of human genetics : EJHG · 2019Article
- A statistical measure for the skewness of X chromosome inactivation based on family trios.BMC genetics · 2018Article
- Next Generation Molecular Diagnosis of Hereditary Spastic Paraplegias: An Italian Cross-Sectional Study.Frontiers in neurology · 2018Article
- S149R, a novel mutation in theOncotarget · 2017Article
- Adrenoleukodystrophy - neuroendocrine pathogenesis and redefinition of natural history.Nature reviews. Endocrinology · 2016Review
- The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis.The application of clinical genetics · 2015Review
- Granny trips down: is she carrying the big bad wolf?Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2013Article
- Clinical manifestations in female carriers of mucopolysaccharidosis type II: a Spanish cross-sectional study.Orphanet journal of rare diseases · 2013Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundApproximately 20% of adrenoleukodystrophy (X-ALD) female carriers may develop clinical manifestations, typically consisting of progressive spastic gait, sensory deficits and bladder dysfunctions. A skewing in X Chromosome Inactivation (XCI), leading to the preferential expression of the X chromosome carrying the mutant ABCD1 allele, has been proposed as a mechanism influencing X-linked adrenoleukodystrophy (X-ALD) carrier phenotype, but reported data so far are conflicting.
methodsTo shed light into this topic we assessed the XCI pattern in peripheral blood mononuclear cells (PBMCs) of 30 X-ALD carriers. Since a frequent problem with XCI studies is the underestimation of skewing due to an incomplete sample digestion by restriction enzymes, leading to variable results, we developed a pyrosequencing assay to identify samples completely digested, on which to perform the XCI assay. Pyrosequencing was also used to quantify ABCD1 allele-specific expression. Moreover, very long-chain fatty acid (VLCFA) levels were determined in the same patients.
resultsWe found severely (≥90:10) or moderately (≥75:25) skewed XCI in 23 out of 30 (77%) X-ALD carriers and proved that preferential XCI is mainly associated with the preferential expression of the mutant ABCD1 allele, irrespective of the manifestation of symptoms. The expression of mutant ABCD1 allele also correlates with plasma VLCFA concentrations.
conclusionsOur results indicate that preferential XCI leads to the favored expression of the mutant ABCD1 allele. This emerges as a general phenomenon in X-ALD carriers not related to the presence of symptoms. Our data support the postulated growth advantage of cells with the preferential expression of the mutant ABCD1 allele, but argue against the use of XCI pattern, ABCD1 allele-specific expression pattern and VLCFA plasma concentration as biomarkers to predict the development of symptoms in X-ALD carriers.
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