A novel sex-determining region on Y (SRY) missense mutation identified in a 46,XY female and also in the father

Mutations in the sex-determining gene SRY previously identified occur in th e 46, XY females. In this study, we investigated whether the SRY mutation p articipates in the onset of XY sex reversal. Genomic deoxyribonucleic acids (DNA) from five XY sex-reversed females were analyzed for mutations in SRY using polymerase-chain reaction (PCR) amplification and subsequent DNA seq uencing. One of the 46, XY females suffered a novel missense mutation at po sition 306 of SRY gene, wherein cytosine was replaced by adenine (CGC-->AGC ), resulting in a substitution of serine for arginine at amino acid positio n 76 of SRY protein. This mutation was located in Helix I of the high-mobil ity-group (HMG) domain. No other mutations were found in the remaining regi ons of the gene. Analysis of the SRY gene in her father revealed that he ca rried the identical mutation version. This substitution introduces a large basic for a small polar uncharged amino acid residue in the HMG box. The fa ct that the father transmits the mutant SRY copy to his offspring implies t hat SRY mutations do not always occur in association with sex reversal, eve n when the ionic environment is altered.