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. © 2007 Wiley-Liss, Inc.
Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation / Tomaselli, Sara; Megiorni, Francesca; Carmelilia De, Bernardo; Aldo, Felici; Giacinto, Marrocco; Giorgio, Maggiulli; Barbara, Grammatico; Daniele, Remotti; Pietro, Saccucci; Ferdinando, Valentini; Mazzilli, Maria Cristina; Silvia, Majore; Grammatico, Paola. - In: HUMAN MUTATION. - ISSN 1059-7794. - STAMPA. - 29:2(2008), pp. 220-226. [10.1002/humu.20665]
Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation
TOMASELLI, SARA;MEGIORNI, Francesca;MAZZILLI, Maria Cristina;GRAMMATICO, Paola
2008
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. © 2007 Wiley-Liss, Inc.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.