title: Two novel SRY missense mutations reducing DNA binding identified in XY females and their mosaic fathers.
abstract: Two novel mutations in the sex-determining gene SRY were identified by screening DNA from 30 sex-reversed XY females by using the SSCP assay. Both point mutations lead to an amino acid substitution in the DNA-binding high-mobility-group domain of the SRY protein. The first mutation, changing a serine at position 91 to glycine, was found in a sporadic case. The second mutation, leading to replacement of a highly conserved proline at position 125 with leucine, is shared by three members of the same family, two sisters and a half sister having the same father. The mutant SRY proteins showed reduced DNA-binding ability in a gel-shift assay. Analysis of lymphocyte DNA from the respective fathers revealed that they carry both the wild-type and the mutant version of the SRY gene. The fact that both fathers transmitted the mutant SRY copy to their offspring implies that they are mosaic for the SRY gene in testis as well as in blood, as a result of a mutation during early embryonic development.
authors.affiliation: Institut für Humangenetik, University of Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmitt-Ney
authors.forename: H
authors.initials: H
authors.lastname: Thiele
authors.forename: P
authors.initials: P
authors.lastname: Kaltwasser
authors.forename: B
authors.initials: B
authors.lastname: Bardoni
authors.forename: M
authors.initials: M
authors.lastname: Cisternino
authors.forename: G
authors.initials: G
authors.lastname: Scherer
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009030:Mosaicism / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D004247:DNA