Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation

Sara Tomaselli, Francesca Megiorni, Carmelilia De Bernardo, Aldo Felici, Giacinto Marrocco, Giorgio Maggiulli, Barbara Grammatico, Daniele Remotti, Pietro Saccucci, Ferdinando Valentini, Maria Cristina Mazzilli, Silvia Majore, Paola Grammatico

Research output: Contribution to journalArticlepeer-review


XX true hermaphroditism, also know as ovotesticular disorder of sexual development (DSD), is a disorder of gonadal development characterized by the presence of both ovarian and testicular tissue in a 46,XX individual. The genetic basis for XX true hermaphroditism and sex reversal syndromes unrelated to SRY translocation is still mostly unclear. We report mutational analysis of the RSPO1 gene in a 46,XX woman with true hermaphroditism, palmoplantar keratoderma, congenital bilateral corneal opacities, onychodystrophy, and hearing impairment. R-spondin1 is a member of the R-spondin protein family and its pivotal role in sex determination has been recently described. We identified a homozygous splice-donor-site mutation in the RSPO1 gene in our patient. We found that the c.286+1G>A mutation led to an aberrantly spliced mRNA (r.95_286del), which is presumably translated into a partially functional protein (p.Ile32_Ile95del). Our case demonstrates for the first time, to our knowledge, that XX true hermaphroditism can be caused by a single gene mutation. The reported findings represent a further step toward a complete understanding of the complex mechanisms leading to DSDs.

Original languageEnglish
Pages (from-to)220-226
Number of pages7
JournalHuman Mutation
Issue number2
Publication statusPublished - Feb 2008


  • β-catenin
  • Development
  • Hermaphroditism
  • R-spondin1
  • RSPO1
  • Splicing mutation
  • XX sex reversal

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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