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Syndromic true hermaphroditism due to an R‐spondin1 ( RSPO1 ) homozygous mutation
Author(s) -
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
Publication year - 2008
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20665
Subject(s) - biology , testis determining factor , true hermaphroditism , mutation , genetics , gene , karyotype , y chromosome , chromosome
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. Hum Mutat 29(2), 220–226, 2008. © 2007 Wiley‐Liss, Inc.