Mutational analysis of patients with X‐linked adrenoleukodystrophy

@article{Kok1995MutationalAO,
  title={Mutational analysis of patients with X‐linked adrenoleukodystrophy},
  author={Fernando Kok and S. Neumann and C O Sarde and S{\'i}qun Lilly Zheng and Kuei‐Hua Wu and Heming Wei and James S. Bergin and Paul A Watkins and Steven J. Gould and George H Sack and Hugo W. Moser and J. L. Mandel and Kirby D. Smith},
  journal={Human Mutation},
  year={1995},
  volume={6}
}
Adrenoleukodystrophy (ALD) is an X‐linked neurodegenerative disorder characterized by elevated very long chain fatty acid (VLCFA) levels, reduced activity of peroxisomal VLCFA‐CoA ligase, and variable phenotypic expression. A putative gene for ALD was recently identified and surprisingly encodes a protein (ALDP) that belongs to a family of transmembrane transporters regulated or activated by ATP (the ABC proteins). We have examined genomic DNA from ALD probands for mutations in the putative ALD… Expand
Mutational and protein analysis of patients and heterozygous women with X-linked adrenoleukodystrophy.
TLDR
The immunodetection of ALDP in white blood cells can be applicable in a majority of ALD kindred, to identify heterozygous women, particularly when the ALD gene mutation has not yet been identified. Expand
Mutational analysis of X-linked adrenoleukodystrophy gene
TLDR
The authors investigated genotype-phenotype correlatons in ALD by analyses on 29 unrelated Japanese patients with ALD and by a review of the literature, finding that no obvious correlations exist between the phenotypes of ALD patients and their geneotypes. Expand
Molecular analysis of ABCD1 gene in Indian patients with X-linked adrenoleukodystrophy.
  • P. Shukla, N. Gupta, +6 authors M. Kabra
  • Biology, Medicine
  • Clinica chimica acta; international journal of clinical chemistry
  • 2011
TLDR
The mutation spectrum of Indian X-ALD patients was identified, which enabled the study to offer accurate genetic counseling, carrier detection and prenatal diagnosis where needed, and to identify significant genotype-phenotype correlation problems. Expand
ABCD1 mutations and the X‐linked adrenoleukodystrophy mutation database: Role in diagnosis and clinical correlations
TLDR
A detailed analysis of all 406 X‐ALD mutations currently included in the database is reported, and 47 novel mutations are presented, including 47 novel extensions of the ABCD1 gene. Expand
A mouse model for X-linked adrenoleukodystrophy.
  • J. F. Lu, A. Lawler, +4 authors K. Smith
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1997
TLDR
It is concluded that X-ald mice exhibit biochemical defects equivalent to those found in human X-ALD and thus provide an experimental system for testing therapeutic intervention. Expand
Targeted inactivation of the X‐linked adrenoleukodystrophy gene in mice
TLDR
Complete absence of ALDP expression results in a VLCFA storage disease but does not impair CNS function of young adult mice by pathologic and clinical criteria, which suggests that additional genetic or environmental conditions must be fulfilled to model the early‐onset and lethality of cerebral ALD in transgenic mice. Expand
Identification of new mutations in Israeli patients with X-linked adrenoleukodystrophy.
TLDR
DNA from blood samples of 7 Jewish and Arab Israeli families suffering from X-linked adrenoleukodystrophy identified five missense-type mutations and a single mutation was identified in three families of Moroccan Jewish descent, probably due to a founder effect. Expand
S149R, a novel mutation in the ABCD1 gene causing X-linked adrenoleukodystrophy
TLDR
It is suggested that the novel mutation, which alters ALDP structure, subcellular distribution and function, is responsible for X-ALD. Expand
Characterization of a novel mutation in exon 10 of the adrenoleukodystrophy gene
TLDR
A novel mutation in the adrenoleukodystrophy gene in skin fibroblasts in primary culture derived from a patient suffering from the adrenocortical insufficiency‐only‐phenotype of ALD is detected, which leads to a translation product lacking the 74 C‐terminal amino acids. Expand
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References

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Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters
ADRENOLEUKODYSTROPHY (ALD) is an X-linked disease affecting 1/20,000 males either as cerebral ALD in childhood or as adrenomyeloneuropathy (AMN) in adults1. Childhood ALD is the more severe form,Expand
Identification of a nonsense mutation in ALD protein cDNA from a patient with adrenoleukodystrophy.
TLDR
This report is the first description of a mutant allele for ALD, at the cDNA level, and presents confirmatory evidence of ALD protein as the primary etiology of ALd. Expand
Abnormal messenger RNA expression and a missense mutation in patients with X-linked adrenoleukodystrophy.
TLDR
Messenger RNA expression in fibroblasts from 6 unrelated ALD patients is reported, providing further evidence that this candidate gene is indeed the ALD gene. Expand
The protein coded by the X‐adrenoleukodystrophy gene is a peroxisomal integral membrane protein
TLDR
Using Western blot analysis of subcellular organelles purified by isopycnic density gradient centrifugation from X‐ALD and control fibroblasts, it is shown that the monoclonal antibodies directed against ALD‐P cross‐react with a 75 kDa protein in intact peroxisomes and that ALD-P is an integral component of theperoxisomal membrane. Expand
The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein.
TLDR
It is shown that the adrenoleukodystrophy protein (ALDP) is associated with the peroxisomal membrane and raised monoclonal antibodies against this protein, that detect a 75kDa band. Expand
Adrenoleukodystrophy: evidence for X linkage, inactivation, and selection favoring the mutant allele in heterozygous cells.
TLDR
The increased levels of fatty acids in plasma in most heterozygotes and the phenotype of blood cells of women heterozygous for both ALD and glucose-6-phosphate dehydrogenase in one family are evidence that selection favoring the mutant allele may occur in vivo as well as in vitro and may explain why many heterozygote manifest clinical symptoms of the disease. Expand
Identification of mutations in the putative ATP-binding domain of the adrenoleukodystrophy gene.
TLDR
Four amino acid substitutions, three frameshift mutations leading to premature termination signal, and a splicing mutation were identified and a nonsense mutation was detected in exon 4 of ALD protein. Expand
Identification of a two base pair deletion in five unrelated families with adrenoleukodystrophy: a possible hot spot for mutations.
TLDR
The identification of a two base pair deletion at position 1801-1802 of the ALD cDNA, located within the fifth exon of theALD gene, which precedes the two consensus motives for ATP-binding, indicating that this position is a hot spot for mutations. Expand
The Prenatal Diagnosis of Adrenoleukodystrophy. Demonstration of Increased Hexacosanoic Acid Levels in Cultured Amniocytes and Fetal Adrenal Gland
TLDR
The capacity to identify the adrenoleukodystrophy hemizygote prenatally together with the availability of tests of plasma and/or cultured skin fibroblasts, which can identify most women heterozygote for this disorder, provide the opportunity for families at risk for ALD to have normal children. Expand
Fatty acid abnormality in adrenoleukodystrophy.
TLDR
This type of fatty acid abnormality has not been described in other pathological conditions and may well represent the unique biochemical abnormality that is directly related to the fundamental genetic defect underlying adrenoleukodystrophy. Expand
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