SUBSTITUTION OF ARGININE-840 BY HISTIDINE IN THE ANDROGEN RECEPTOR OFA FAMILY WITH REIFENSTEIN SYNDROME

In a large kindred with Reifenstein syndrome, we performed the molecul ar analysis of the androgen receptor gene. Since the biochemical chara cteristics of the androgen receptor, determined on the cultured genita l skin fibroblasts, showed a drastic decrease of the androgen binding capacity, we assumed that a point mutation was located in exons 4-8 en coding the carboxy-terminal domain of the receptor. Enzymatic amplific ations of these exons did not point out any deletions. Direct sequenci ng showed a G-A point mutation at position 2818 of exon 7 responsible for an arginine-histidine substitution at position 840 of the androgen receptor. The presence of the same mutation has been reported by othe r groups in four unrelated patients. Its association with different ph enotypes of androgen insensitivity and different biochemical character istics of the androgen receptor pointed out the complexity of the geno type-phenotype relationship in androgen insensitivity, Moreover the id entification of the point mutation gave us the opportunity to perform a prenatal exclusion diagnosis of Reifenstein syndrome in this high-ri sk family.