Candidate genes in complete and partial XY sex reversal: mutation analysis of SRY, SRY-related genes and FTZ-F1.
The sexual phenotype is established in three steps: (1) the sex chromosome constitution; (2) the differentiation of the gonads; and (3) the response of the internal and external genitalia to the hormones produced by the differentiated gonads. Errors that occur at any of these stages can result in defective sexual differentiation. Therefore the investigation of patients with abnormalities of testis development will help elucidate the mechanisms of sex determination and gonadal differentiation. It was in this way that SRY. the primary testis determining gene was identified. De novo mutations in SRY, result in gonadal dysgenesis by disrupting the DNA-binding activity of the SRY protein. However, only 20% of cases of gonadal dysgenesis, are explained by mutations in SRY or its flanking sequences. Therefore, there are several pieces to this puzzle yet to be discovered and it is hoped that mutation analysis of other genes implicated in gonadal development and differentiation may shed some light on aetiology of gonadal dysgenesis in the remaining 80% of cases.
Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, UK.
H N
HN
Lim
S H
SH
Freestone
D
D
Romero
C
C
Kwok
I A
IA
Hughes
J R
JR
Hawkins
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D012734:Disorders of Sex Development; D051717:Fushi Tarazu Transcription Factors; D018628:Gene Dosage; D006059:Gonadal Dysgenesis / Q000196:embryology / Q000235:genetics*; D018398:Homeodomain Proteins; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012733:Sex Differentiation; D051876:Sex-Determining Region Y Protein; D054339:Steroidogenic Factor 1; D013737:Testis / Q000002:abnormalities; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; C497746:Sry protein, mouse; D054339:Steroidogenic Factor 1; D014157:Transcription Factors