Available Assays

Molecular genetic testing of the ABCD1 gene is available clinically from a few laboratories. Because many of the mutations identified are private mutations specific to a particular family, PCR amplification and SSCP or direct sequencing of all 10 exons has been used successfully to identify mutations in the majority of cases,28 whereas Southern blotting can be used to assess deletion and duplication status as long as the rearrangement is small enough to be detected with gene-specific probes. Complications can arise during PCR amplification due to the presence of paralogous gene segments of ABCD1 spanning exons 7 to 10 on chromosomes 2p11,10p11,16p11,and 22q11,but can be overcome by choice of primers that avoids amplification from the other chromosomes.28 Although mutations have been identified throughout the entire ABCD1 gene, a 2 bp AG deletion in exon 5 was found in 10.3% of families with X-ALD and is therefore the most common mutation identified in the ABCD1 gene.29 Interestingly, this mutation, which is associated with all X-ALD phenotypes, does not represent a founder allele and is therefore a mutation hotspot within the ABCD1 gene.

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