Twenty-five of the ALD probands whose ALD genes appeared normal by Southern blot analysis were surveyed for mutations by Single Strand Conformation Polymorphism (SSCP) procedures and DNA sequence analysis.
The disruptive nature of two mutations (i.e., the frameshift and the nonsense mutation) in patients with biochemically proved childhood ALD and AMN further strongly supports the hypothesis that alterations in this gene play a crucial role in the pathogenesis of X-ALD.
This study reports that the retroviral-mediated transfer of the ALD cDNA restored very-long-chain fatty acid oxidation in ALD fibroblasts in vitro following abundant expression and appropriate targeting of the vector-encoded ALDP in peroxisomes.
To determine whether mutations occur in the putative NBF of ALD protein, we analyzed by denaturing gradient gel electrophoresis (DGGE) exon 6 and 8 that encode most part of this domain in 50 ALD patients.
Since 5%-15% of heterozygous women have normal VLCFA levels, 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.
Since 5%-15% of heterozygous women have normal VLCFA levels, 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.
ALD shows a highly variable phenotypic expression and extensive mutation analysis in ALD patients has failed to establish a genotype-phenotype correlation, even in the presence of the same ALD-gene defect.
These results provide the first evidence of both homo- and heterodimerization of mammalian ABC half-transporters and suggest that the loss of ALDP dimerization plays a role in X-ALD pathogenesis.
Expression studies revealed that only K217E is a deleterious mutation, because a plasmid encoding ALDP with K217E was ineffective in the restoration of defective beta-oxidation in X-ALD fibroblasts.
Taken together, our data suggest that some less severe or late-onset forms of X-ALD associated with splice mutations result from the production of small amounts of normal ALDP.
Taken together, our data suggest that some less severe or late-onset forms of X-ALD associated with splice mutations result from the production of small amounts of normal ALDP.
Adding new variants to the repertoire of ABCD1 mutations in X-ALD, our data provide an efficient, cost-effective, and reliable DHPLC detection protocol for mutation screening of X-ALD families.
X-linked adrenoleukodystrophy in Spain. Identification of 26 novel mutations in the ABCD1 gene in 80 patients. Improvement of genetic counseling in 162 relative females.