DNA-BASED DIAGNOSTICS FOR ADRENOLEUKODYSTROPHY IN A LARGE NEW-ZEALANDFAMILY

Aim. 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 P CR amplified products encompassing defined exons of the ALD gene. The identification of a mutation led to the development of a simple restri ction enzyme digestion protocol of a PCR amplified product to identify those individuals with the mutation. Results. A nonsense mutation, re sulting in deduced premature termination of translation of the ALD gen e 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 A LD family. A DNA-based test was established to identify this mutation by Bgl II digestion of a PCR amplified product encompassing exons 3 an d 4 of the ALD gene. The DNA-based test was applied to a chorionic vil lus sampling for prenatal diagnosis. Conclusions. A simple DNA-based t est has been developed for ALD in a large New Zealand family. This tes t provides a rapid means of determining carrier status and for underta king prenatal diagnosis for ALD in this family.