title: XY sex reversal associated with a nonsense mutation in SRY.
abstract: Sex determination in humans is mediated through the expression of a testis-determining gene on the Y chromosome. In humans, a candidate gene for the testis-determining factor (TDF) that encodes a protein with a putative DNA-binding motif and has been isolated is termed SRY. Here we describe an XY sex-reversed female with pure gonadal dysgenesis who harbors a de novo nonsense mutation in the SRY open reading frame (SRY-orf). This single-basepair substitution results directly in the formation of a termination codon in the putative SRY DNA-binding motif, presumably leading to a nonfunctional gene product. This brings the number of reported XY sex-reversed females with de novo mutations in the known SRY-orf to three, each occurring in the putative DNA-binding domain. This provides further evidence to support SRY being TDF in humans and also indicates the functional importance of the putative DNA-binding domain of the SRY protein.
authors.affiliation: Unité INSERM U276, Université Paris VII, France.
authors.forename: K D
authors.initials: KD
authors.lastname: McElreavey
authors.forename: E
authors.initials: E
authors.lastname: Vilain
authors.forename: C
authors.initials: C
authors.lastname: Boucekkine
authors.forename: M
authors.initials: M
authors.lastname: Vidaud
authors.forename: F
authors.initials: F
authors.lastname: Jaubert
authors.forename: F
authors.initials: F
authors.lastname: Richaud
authors.forename: M
authors.initials: M
authors.lastname: Fellous
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D012734:Disorders of Sex Development; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics* / Q000473:pathology; D006066:Gonads / Q000473:pathology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010375:Pedigree; D014960:X Chromosome; D014998:Y Chromosome
chemical_list: D004247:DNA