Xp duplications and sex reversal.
Male to female sex reversal has been observed in individuals with duplications of the short arm of the X chromosome. The study of Xp duplicated patients demonstrated that sex reversal results from the presence of two active copies of the DSS (dosage sensitive sex reversal) locus. A double dosage of DSS disrupts testis formation whereas its absence is compatible with a male phenotype, suggesting a role for DSS in ovarian development and as a link between ovary and testis formation. DSS was localized to a 160 kb region of Xp21, overlapping the adrenal hypoplasia congenita locus. The search for expressed sequences in the DSS critical region led to the identification of two types of genes: the DAM family and DAX-1, an atypical member of the nuclear receptor superfamily. Although no function is currently known for DAM genes, functional deficiency for DAX-1 has been shown to be responsible for adrenal hypoplasia congenita and hypogonadotropic hypogonadism. The search for the DSS gene(s) is still open and both the DAM genes and DAX-1 represent DSS candidate genes.
Zanaria
E
E
Università di Pavia, Italy.
Bardoni
B
B
Dabovic
B
B
Calvari
V
V
Fraccaro
M
M
Zuffardi
O
O
Camerino
G
G
D000309:Adrenal Insufficiency / Q000196:embryology / Q000503:physiopathology; D002874:Chromosome Mapping; D012734:Disorders of Sex Development; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D006066:Gonads / Q000196:embryology / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D007006:Hypogonadism / Q000196:embryology / Q000503:physiopathology; D008297:Male; D010641:Phenotype; D012729:Sex Chromosome Aberrations / Q000235:genetics; D012733:Sex Differentiation; D014960:X Chromosome / Q000235:genetics*