Mutation analysis of the gene involved in adrenoleukodystrophy
- Univ. Hospital Nijmegen (Netherlands)
- Academic Medical Center, Amsterdam (Netherlands)
A gene responsible for the X-linked genetic disorder adrenoleukodystrophy (ALD) that is characterized by demyelination of the nervous system and adrenocortical insufficiency has been identified by positional cloning. The gene encodes an ATP-binding transporter which is located in the peroxisomal membrane. Deficiency of the gene leads to accumulation of unsaturated very long chain fatty acids due to impaired peroxisomal {beta}-oxidation. A systematic analysis of the open reading frame of the ALD gene unraveled the mutations in 28 different families using reverse transcriptase-PCR followed by direct sequencing. No entire gene deletions or drastic promoter mutations have been detected. Only in one family did the mutation involved multiple exons. The remaining mutations were subtle alterations leading to missense (about 50%) or nonsense mutations, frameshifts or splice acceptor site defects. In one patient a single codon was missing. Mutations affecting a single amino acid were concentrated in the region between the third and fourth putative membrane spanning fragments and in the ATP-binding domain. This overview of mutations aids in the determination of structural and functional important regions and facilitates the screening for mutations in other ALD patients. The detection of mutations in virtually all ALD families tested indicates that the isolated gene is the only gene responsible for ALD located in Xq28.
- OSTI ID:
- 134349
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1082
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
GENES
GENE MUTATIONS
STRUCTURE-ACTIVITY RELATIONSHIPS
DNA-CLONING
SPLICING
SCREENING
DETECTION
NERVOUS SYSTEM DISEASES
PATIENTS
HEREDITARY DISEASES
HUMAN X CHROMOSOME
GENETIC MAPPING
CARBOXYLIC ACIDS
METABOLISM
DNA SEQUENCING
CODONS
AMINO ACIDS
POLYMERASE CHAIN REACTION
EXONS