R-spondin1 is essential in sex determination, skin differentiation and malignancy.
R-spondins are a recently characterized small family of growth factors. Here we show that human R-spondin1 (RSPO1) is the gene disrupted in a recessive syndrome characterized by XX sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Our data show, for the first time, that disruption of a single gene can lead to complete female-to-male sex reversal in the absence of the testis-determining gene, SRY.
Parma
Pietro
P
Dipartimento di Patologia Umana ed Ereditaria, Sezione di Biologia Generale e Genetica Medica, Università di Pavia, Via Forlanini 14, 27100 Pavia, Italy.
Radi
Orietta
O
Vidal
Valerie
V
Chaboissier
Marie Christine
MC
Dellambra
Elena
E
Valentini
Stella
S
Guerra
Liliana
L
Schedl
Andreas
A
Camerino
Giovanna
G
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D012734:Disorders of Sex Development; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009154:Mutation; D010375:Pedigree; D019849:Sex Determination Processes; D012867:Skin / Q000166:cytology* / Q000196:embryology; D012878:Skin Neoplasms / Q000235:genetics*; D019699:Thrombospondins / Q000235:genetics* / Q000502:physiology*; D000098907:R-Spondins
D019699:Thrombospondins; C503243:RSPO1 protein, human; D000098907:R-Spondins