title: A novel double nucleotide substitution in the HMG box of the SRY gene associated with Swyer syndrome.
abstract: We describe a novel double nucleotide substitution in the SRY gene of a 46,XY female with gonadal dysgenesis or Swyer syndrome. The SRY sequence was analysed by both the single-strand conformational polymorphism assay and direct DNA sequencing of products from the polymerase chain reaction. A double nucleotide substitution was identified at codon 18 of the conserved HMG box motif, causing an arginine to asparagine amino acid substitution. The altered residue is situated in the high mobility group (HMG)-related box of the SRY protein, a potential DNA-binding domain. Since the mutation abolishes one HhaI recognition site, the results were confirmed by HhaI restriction mapping. No other mutations were found in the remaining regions of the gene. The corresponding DNA region from the patient's brother was analysed and found to be normal. We conclude that the SRY mutation in the reported XY female occurred de novo and is associated with sex reversal.
authors.affiliation: Dipartimento di Medicina Sperimentale, Università di L'Aquila, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Battiloro
authors.forename: B
authors.initials: B
authors.lastname: Angeletti
authors.forename: M C
authors.initials: MC
authors.lastname: Tozzi
authors.forename: L
authors.initials: L
authors.lastname: Bruni
authors.forename: S
authors.initials: S
authors.lastname: Tondini
authors.forename: P
authors.initials: P
authors.lastname: Vignetti
authors.forename: R
authors.initials: R
authors.lastname: Verna
authors.forename: E
authors.initials: E
authors.lastname: D'Ambrosio
mesh_terms: D000328:Adult; D001120:Arginine; D001216:Asparagine; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005796:Genes / Q000235:genetics; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics*; D006609:High Mobility Group Proteins / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins; 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; D001216:Asparagine; D001120:Arginine; D015252:Deoxyribonucleases, Type II Site-Specific; C037130:GCGC-specific type II deoxyribonucleases