DNA-based diagnostics for adrenoleukodystrophy in a large New Zealand family.
OBJECTIVE
To develop a DNA-based diagnostic test for adrenoleukodystrophy (ALD) in a large New Zealand family.


METHODS
Mutation screening of the X chromosome-linked ALD gene was undertaken by direct sequencing of PCR amplified products encompassing defined exons of the ALD gene. The identification of a mutation led to the development of a simple restriction enzyme digestion protocol of a PCR amplified product to identify those individuals with the mutation.


RESULTS
A nonsense mutation, resulting in deduced premature termination of translation of the ALD gene product, was detected in exon 4 of the ALD gene in an affected male. This mutation was found in three obligate gene carriers in the same ALD family. A DNA-based test was established to identify this mutation by Bgl II digestion of a PCR amplified product encompassing exons 3 and 4 of the ALD gene. The DNA-based test was applied to a chorionic villus sampling for prenatal diagnosis.


CONCLUSIONS
A simple DNA-based test has been developed for ALD in a large New Zealand family. This test provides a rapid means of determining carrier status and for undertaking prenatal diagnosis for ALD in this family.
Rowland
S A
SA
School of Biological Sciences, University of Auckland.
Dodd
A
A
Roche
A L
AL
Manilal
S
S
Kennedy
M A
MA
Becroft
D M
DM
Tonkin
S
S
Chapman
C
C
Love
D R
DR
D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015193:Chorionic Villi Sampling; D018389:Codon, Nonsense / Q000235:genetics; D004247:DNA / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D008040:Genetic Linkage / Q000235:genetics; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D009520:New Zealand; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D014960:X Chromosome / Q000235:genetics
D018389:Codon, Nonsense; D004247:DNA