X-linked adrenoleukodystrophy (ALD): A novel mutation of the ALD gene in 6 members of a family presenting with 5 different phenotypes
Abstract
Fragments of the adrenoleukodystrophy (ALD) cDNA from a patient with adolescent ALD were amplified by polymerase chain reaction and subcloned. Bidirectional sequencing of the entire coding ALD gene disclosed a cytosine to guanine transversion at nucleotide 1451 in exon five, resulting in substitution of proline 484 by arginine. Five of nine siblings of the patient, comprising two cerebral ALD, one adrenomyeloneuropathy, one Addison only as well as the symptomatic mother (all accumulating very long chain fatty acids) carried this mutation, which was not found in the unaffected persons, in five unrelated ALD patients, and in twenty controls. We propose that this missense mutation generated the disease per se as well as the metabolic defect; the different phenotypes, however, must have originated by means of additional pathogenetic factors.
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Devastating childhood cALD and late adulthood AMN may co-exist within the same family.
“Devastating childhood cALD and late adulthood AMN may co-exist within the same family [103,104,105,106], whereas the few studied monozygotic twins showed less discordant phenotypes [107,108,109,110].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [103]
Males in the same family may express different X-ALD phenotypes.
“Males in the same family may express different phenotypes [Berger et al., 1994;Moser et al., 2001].”
From ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: Role in diagnosis and clinical correlations (2001) · cites this paper as Berger et al., 1994
Five different phenotypes in six male patients of a family with the destabilizing missense mutation P484R demonstrate the lack of genotype-phenotype correlation in X-ALD.
“Another striking demonstration of the lack of genotype-phenotype correlation is the presence of five different phenotypes in six male patients of a family with a destabilizing missense mutation, P484R [Berger et al., 1994].”
From ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: Role in diagnosis and clinical correlations (2001) · cites this paper as Berger et al., 1994
Within individual kindreds, phenotypes of the entire clinical spectrum of X-ALD have been described.
“Secondly, within individual kindreds, phenotypes of the entire clinical spectrum of X-ALD have been described.15,32,33”
From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [32]
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“Both phenotypes can occur within the same kindred [121] and no general genotype–phenotype correlation exists for the severity in X-ALD [122–125].”
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X-linked adrenoleukodystrophy phenotype is independent of ABCD2 genotype
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- Authors
- Berger, J., Molzer, B., Fae, I., & Bernheimer, H.
- Affiliations
- University of Vienna (AT)
- ORCID
- Berger, J.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 1994-12
- Volume
- 205
- Issue
- 3
- Pages
- 1638-1643
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2095072855
- Cited by
- 126
- References
- 0
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 4 · 2014: 3 · 2013: 3 · 2012: 3
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- X-linked adrenoleukodystrophy, missense mutations, very long chain fatty acids, adrenomyeloneuropathy, cerebral adrenoleukodystrophy, Addison's disease, genotype-phenotype correlation
- MeSH terms
- Adolescent, Adrenoleukodystrophy, Adult, Base Sequence, Child, Cloning, Molecular, Exons, Female, Humans, Genetic Linkage, Male, Molecular Sequence Data, Pedigree, Phenotype, X Chromosome, Point Mutation, DNA Primers, DNA, Complementary
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