Objectives: We report the unusual phenotypic expression in 2 female carriers of a family with X-linked recessive bulbospinal neuronopathy (X-BSN). We analyze the methylation pattern of the androgen receptor (AR) gene to inspect the possibility of non-random X chromosome inactivation to be the underlying mechanism.
Material and methods: Twenty-three members in 3 generations of a Taiwanese family were examined and studied for genomic DNA analysis. We analyzed the sequence of the first exon of the AR gene to identify the numbers of CAG repeats, and to determine the methylation pattern by using the restriction enzymes HpaII and HhaI.
Results: There were 3 probands and 5 carriers and 2 of the carriers manifested clinical symptoms. Sequence analysis revealed that the numbers of trinucleotide repeats ranged from 42 to 45 in one allele of the X-chromosome in the 5 female carriers. The restriction pattern of the HpaII and HhaI recognizable sites of the X-chromosome indicated a random methylation.
Conclusion: Our data suggest that molecular genetic studies are important in confirming the diagnosis of X-BSN and early detection of female carriers, and the random or non-random methylation pattern of the X-chromosome is not a determining factor for partial expression of the abnormal AR gene in some carriers.