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R-spondin1 tips the balance in sex determination

Nature Genetics volume 38, pages 1233–1234 (2006)Cite this article

Female-to-male sex reversal is an extremely rare and puzzling phenomenon. A new study identifies mutations in the gene encoding R-spondin1 in XX sex-reversed individuals and suggests that antagonistic pathways in the bipotential gonad regulate sex determination.

On page 1304 of this issue, Pietro Parma and colleagues1 describe a recessive mutation in the gene encoding R-spondin1 (RSPO1) that results in complete female-to-male sex reversal associated with palmoplantar hyperkeratosis (PPK) and predisposition to squamous cell carcinoma of the skin. The authors mapped the gene in a consanguineous family informative for linkage analysis of the PPK trait, and they identified a single nucleotide insertion leading to a frameshift and stop codon in RSPO1. They confirmed the identity of the gene in a second independent case of the syndrome in which the affected XX male (shown to have a different haplotype) was found to carry a homozygous deletion within RSPO1. These data provide strong evidence that RSPO1 is the gene responsible for this complex syndrome.

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  1. Department of Cell Biology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Blanche Capel

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Capel, B. R-spondin1 tips the balance in sex determination. Nat Genet 38, 1233–1234 (2006). https://doi.org/10.1038/ng1106-1233

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