Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters

@article{Mosser1993PutativeXA,
  title={Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters},
  author={Jean Mosser and Anne Douar and C O Sarde and Petra Kioschis and Robert Feil and Hugo W. Moser and Annemarie Poustka and J. L. Mandel and Patrick Aubourg},
  journal={Nature},
  year={1993},
  volume={361},
  pages={726-730}
}
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, with onset of neurological symptoms between 5–12 years of age. Central nervous system demyelination progresses rapidly and death occurs within a few years. AMN is a milder form of the disease with onset at 15–30 years of age and a more progressive course. Adrenal insufficiency (Addison's disease) may… Expand
X‐Linked Adrenoleukodystrophy
TLDR
The mechanisms that lead to the inflammatory reaction in cerebral ALD might involve abnormal acylation of gangliosides and phospholipids by VLCFA that would result in immune reaction of brain macrophages and astrocytes bearing CD1 molecules that recognize lipid antigens. Expand
Molecular Genetics of X‐linked Adrenoleukodystrophy
TLDR
The clinical spectrum of X-ALD ranges from a progressive myelopathy (adrenomyeloneuropathy) in adult males and females to a fatal cerebral demyelinating disease in boys and adult males (cerebral ALD). Expand
Pathophysiology of X-linked adrenoleukodystrophy q
Currently the molecular basis for the clinical heterogeneity of X-linked adrenoleukodystrophy (X-ALD) is poorly understood. The genetic bases for all different phenotypic variants of X-ALD areExpand
cDNA sequence of Aldgh, the mouse homolog of the X-linked adrenoleukodystrophy gene
TLDR
The sequence of the mouse ALD cDNA (Aldh) and data suggesting that homologous sequences are present in a wide range of species are reported here, and it is suggested that homology to ATP-binding domains of proteins such as CFTR or the multidrug resistance glycoprotein (MDR1) is present. Expand
Therapy of X-linked adrenoleukodystrophy
TLDR
Gene therapy of endogenous hematopoietic stem cells, pharmacological upregulation of other genes encoding proteins involved in peroxisomal β-oxidation, reduction of oxidative stress, and possibly lovastatin are candidates for future X-ALD therapies. Expand
Adrénoleucodystrophie liée à l'X
TLDR
X-linked adrenoleukodystrophy is a severe neurodegenerative disorder characterized by progressive demyelination within the central and peripheral nervous system, adrenal insufficiency, and accumulation of very-long-chain fatty acids (VLCFA) in plasma, fibroblasts and tissues. Expand
X-linked adrenoleukodystrophy: clinical, biochemical and pathogenetic aspects.
TLDR
Different molecular mechanisms seem to induce inflammatory demyelination, neurodegeneration and adrenocortical insufficiency involving the primary ABCD1 defect, environmental factors and modifier genes involved in X-linked adrenoleukodystrophy. Expand
X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects.
TLDR
Environmental factors and a multitude of modifying genes appear to determine the clinical manifestation in this monogenetic but multifactorial disease. Expand
Adrénoleucodystrophie liée à l’X X-linked adrenoleukodystrophy
X-linked adrenoleukodystrophy (ALD) is a severe neurodegenerative disorder. ALD is characterized by progressive demyelination within the central and peripheral nervous system, adrenal insufficiencyExpand
X-linked Adrenoleukodystrophy
TLDR
The main biochemical defect is the accumulation of very-long-chain fatty acids (VLCFA, fatty acids with a chain length of more than 22 carbon atoms), particularly in the cholesterol ester fraction of the adrenal gland and brain white matter. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 35 REFERENCES
The red-green visual pigment gene region in adrenoleukodystrophy.
TLDR
It is proposed that a single DNA rearrangement could underlie both ALD and abnormal color vision in patients with adrenomyeloneuropathy, and that the frequent phenotypic color vision anomalies owe their origin to deleted DNA that includes regulatory genes for color vision. 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
Peroxisomal lignoceroyl-CoA ligase deficiency in childhood adrenoleukodystrophy and adrenomyeloneuropathy.
TLDR
The pathognomonic accumulation of very long chain fatty acids in C-ALD and AMN is due to a deficiency of peroxisomalvery long chain (lignoceric acid) acyl-CoA ligase. Expand
Adrenoleukodystrophy: a complex chromosomal rearrangement in the Xq28 red/green-color-pigment gene region indicates two possible gene localizations.
TLDR
A complex chromosomal rearrangement in band Xq28 is characterized in an adrenoleukodystrophy patient who also has blue-cone monochromacy and includes two deletions, most likely separated by a large (greater than 110-kb) inversion. Expand
Linkage of adrenoleukodystrophy to a polymorphic DNA probe
TLDR
These data permit assignment of adrenoleukodystrophy carrier status in family members at risk, supplementing the chemical measurement of very‐long‐chain fatty acids. Expand
Frequent alterations of visual pigment genes in adrenoleukodystrophy.
TLDR
Study of the red and green visual pigment genes in eight ALD kindreds has shown frequent structural changes including deletions and possible intragenic recombinations that should help define both the structural gene responsible for ALD and physical genetic relationships in the Xq28 region. Expand
Mutations in the 70K peroxisomal membrane protein gene in Zellweger syndrome
TLDR
It is suggested that PMP 70 plays an important role in peroxisome biogenesis and that mutations in PMP70 may be responsible for a subset of ZS patients. Expand
Lignoceric acid is oxidized in the peroxisome: implications for the Zellweger cerebro-hepato-renal syndrome and adrenoleukodystrophy.
TLDR
It is found that normal hepatocellular peroxisomes are found in the liver biopsy of a childhood ALD patient and the oxidation of palmitic acid in cultured skin fibroblasts was inhibited by 62% in control and X chromosome-linked ALD patients compared with 88% in CHRS and neonatal ALD. Expand
A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein
TLDR
A cluster of four mutations was discovered in a 30-base-pair region of exon 11 of CFTR, which reveal a functionally important region in the CFTR protein and provide further evidence that CFTR is a member of the family of ATP-dependent transport proteins. Expand
Identification of a chromosome 18q gene that is altered in colorectal cancers.
TLDR
A contiguous stretch of DNA comprising 370 kilobase pairs has now been cloned from a region of chromosome 18q suspected to reside near the DCC gene, which may play a role in the pathogenesis of human colorectal neoplasia, perhaps through alteration of the normal cell-cell interactions controlling growth. Expand
...
1
2
3
4
...