title: Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation.
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.
authors: Medical Genetics, Experimental Medicine Department, Sapienza-University of Rome, Rome, Italy.
authors: Sara
authors: S
authors: Tomaselli
authors: Francesca
authors: F
authors: Megiorni
authors: Carmelilia
authors: C
authors: De Bernardo
authors: Aldo
authors: A
authors: Felici
authors: Giacinto
authors: G
authors: Marrocco
authors: Giorgio
authors: G
authors: Maggiulli
authors: Barbara
authors: B
authors: Grammatico
authors: Daniele
authors: D
authors: Remotti
authors: Pietro
authors: P
authors: Saccucci
authors: Ferdinando
authors: F
authors: Valentini
authors: Maria Cristina
authors: MC
authors: Mazzilli
authors: Silvia
authors: S
authors: Majore
authors: Paola
authors: P
authors: Grammatico
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D006066:Gonads / Q000166:cytology; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D050090:Ovotesticular Disorders of Sex Development / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013577:Syndrome; D019699:Thrombospondins / Q000737:chemistry / Q000235:genetics*; D000098907:R-Spondins
chemical_list: D012333:RNA, Messenger; D019699:Thrombospondins; C503243:RSPO1 protein, human; D000098907:R-Spondins