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 journalArticle

106 Citations (Scopus)

Abstract

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
Volume29
Issue number2
DOIs
Publication statusPublished - Feb 2008

Fingerprint

Ovotesticular Disorders of Sex Development
vpr Genes
Mutation
Gonadal Disorders
Palmoplantar Keratoderma
Corneal Opacity
Disorders of Sex Development
RNA Splice Sites
Hearing Loss
Proteins
Messenger RNA
Genes

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Tomaselli, S., Megiorni, F., De Bernardo, C., Felici, A., Marrocco, G., Maggiulli, G., ... Grammatico, P. (2008). Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation. Human Mutation, 29(2), 220-226. https://doi.org/10.1002/humu.20665

Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation. / Tomaselli, Sara; Megiorni, Francesca; De Bernardo, Carmelilia; Felici, Aldo; Marrocco, Giacinto; Maggiulli, Giorgio; Grammatico, Barbara; Remotti, Daniele; Saccucci, Pietro; Valentini, Ferdinando; Mazzilli, Maria Cristina; Majore, Silvia; Grammatico, Paola.

In: Human Mutation, Vol. 29, No. 2, 02.2008, p. 220-226.

Research output: Contribution to journalArticle

Tomaselli, S, Megiorni, F, De Bernardo, C, Felici, A, Marrocco, G, Maggiulli, G, Grammatico, B, Remotti, D, Saccucci, P, Valentini, F, Mazzilli, MC, Majore, S & Grammatico, P 2008, 'Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation', Human Mutation, vol. 29, no. 2, pp. 220-226. https://doi.org/10.1002/humu.20665
Tomaselli S, Megiorni F, De Bernardo C, Felici A, Marrocco G, Maggiulli G et al. Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation. Human Mutation. 2008 Feb;29(2):220-226. https://doi.org/10.1002/humu.20665
Tomaselli, Sara ; Megiorni, Francesca ; De Bernardo, Carmelilia ; Felici, Aldo ; Marrocco, Giacinto ; Maggiulli, Giorgio ; Grammatico, Barbara ; Remotti, Daniele ; Saccucci, Pietro ; Valentini, Ferdinando ; Mazzilli, Maria Cristina ; Majore, Silvia ; Grammatico, Paola. / Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation. In: Human Mutation. 2008 ; Vol. 29, No. 2. pp. 220-226.
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