Atypical Features in a Spinal and Bulbar Muscular Atrophy Patient with a 68 CAG Repeat (P1.087)

Objective: To describe the clinical features and disease presentation in a patient with spinal and bulbar muscular atrophy (SBMA) who has an unusually large CAG repeat expansion of 68. Background: SBMA is an X-linked motor neuron disease caused by a trinucleotide (CAG) repeat expansion within the androgen receptor gene. Patients with the disease have weakness, atrophy, and fasciculations in the limb and bulbar muscles. The disease occurs when the CAG repeat length increases to between 38 and 62 CAGs from a normal length of between 11 and 32 CAGs. Patients with CAG repeat lengths greater than 62 have not previously been reported. Design/Methods: We evaluated a 29 year old SBMA patient with 68 CAGs at the National Institutes of Health. History and physical examination were obtained, and muscle strength and function were assessed. DNA from the subject’s blood and fibroblasts were analyzed. Evaluation of androgen receptor expression in the fibroblasts was performed in comparison to control samples. Results: PCR amplification and sequencing of the androgen receptor gene confirmed a repeat length of 68 CAGs in both the blood and fibroblasts. Quantitative PCR and western blot analysis of patient fibroblasts showed levels of androgen receptor mRNA and protein equivalent to control samples. Evaluation of muscle and sensory function showed deficits typical for the disease. In addition, the patient had manifestations of small fiber neuropathy and abnormal sexual development. Conclusions: These findings expand the known phenotype associated with SBMA and shed new insights into the effects of the mutated androgen receptor. Disclosure: Dr. Grunseich has nothing to disclose. Dr. Kats has nothing to disclose. Dr. Bott has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Kokkinis has nothing to disclose. Dr. Rinaldi has nothing to disclose. Dr. Fischbeck has nothing to disclose.