X-LINKED RECESSIVE BULBOSPINAL NEURONOPATHY - CLINICAL AND MOLECULAR STUDIES IN A TAIWANESE FAMILY

We describe clinical, biochemical, and molecular studies on a Taiwanes e family with X-linked recessive bulbospinal neuronopathy. There were three probands and five female carriers among the 23 members examined. The clinical manifestations included progressive muscle weakness, dif fuse fasciculation, postural tremor, muscle cramps, dysarthria, dyspha gia, diabetes, and gynecomastia. Phenotypic expression varied among th e affected subjects. Two carriers also had postural tremor and periora l fasciculation. Endocrine tests were normal except for a mild increas e in serum testosterone and/or growth hormone in one patient and one c arrier. Type IV hyperlipoproteinemia was observed in two patients, one carrier, and one healthy offspring. Molecular genetic studies confirm ed elongation of the CAG triplet repeat in exon 1 of the gene for the androgen receptor. Sequence analysis showed that there were 42 to 43 C AG repeats in the three probands and 42 to 45 in the five carriers. Th e mutant allele had a tendency to increase by one or two repeats from one generation to the next. The length of CAG repeats at which the mut ant allele became unstable was shorter in our family than in previous reports. The normal allele was also unstable and had a tendency to shr ink by one to five repeats during transmission. These findings suggest that the number of CAG triplet repeats is variable in both the mutant and normal alleles.