title: A novel sex-determining region on Y (SRY) missense mutation identified in a 46,XY female and also in the father.
abstract: Mutations in the sex-determining gene SR Y previously identified occur in the 46, XY females. In this study, we investigated whether the SR Y mutation participates in the onset of XY sex reversal. Genomic deoxyribonucleic acids (DNA) from five XY sex-reversed females were analyzed for mutations in SR Y using polymerase-chain reaction (PCR) amplification and subsequent DNA sequencing. One of the 46, XY females suffered a novel missense mutation at position 306 of SR Y gene, wherein cytosine was replaced by adenine (CGC-->AGC), resulting in a substitution of serine for arginine at amino acid position 76 of SR Y protein. This mutation was located in Helix I of the high-mobility-group (HMG) domain. No other mutations were found in the remaining regions of the gene. Analysis of the SR Y gene in her father revealed that he carried the identical mutation version. This substitution introduces a large basic for a small polar uncharged amino acid residue in the HMG box. The fact that the father transmits the mutant SR Y copy to his offspring implies that SR Y mutations do not always occur in association with sex reversal, even when the ionic environment is altered.
authors.affiliation: Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Imai
authors.forename: A
authors.initials: A
authors.lastname: Takagi
authors.forename: T
authors.initials: T
authors.lastname: Tamaya
mesh_terms: D000328:Adult; D004247:DNA / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D006609:High Mobility Group Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009687:Nuclear Proteins; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D019849:Sex Determination Processes; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D004247:DNA