NORMAL ERYTHROCYTE-MEMBRANE GS-ALPHA BIOACTIVITY IN 2 UNRELATED PATIENTS WITH ACRODYSOSTOSIS

Shortening of the tubular bones of the hands and feet with cone shaped epiphyses is known as peripheral dysostosis and is common to several syndromes including acrodysostosis and Albright's hereditary osteodyst rophy (AHO). The underlying defect in AHO is known to be a reduction i n bioactivity of the alpha subunit of the signal transducing protein, Gs, and heterozygous deactivating mutations have been shown in the Gs alpha gene. Because of additional overlapping clinical and radiologica l features it has been suggested that acrodysostosis and AHO represent poles of a single diagnostic spectrum. We have measured Gs alpha bioa ctivity in two unrelated patients with a clinical diagnosis of acrodys ostosis and found both to be normal. Mutation analysis of the Gs alpha gene showed no sequence variation in 12 of the 13 exons examined. The se results indicate that, at least in a proportion of patients with ac rodysostosis, the condition is aetiologically distinct from AHO.