Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation.
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.
Tomaselli
Sara
S
Medical Genetics, Experimental Medicine Department, Sapienza-University of Rome, Rome, Italy.
Megiorni
Francesca
F
De Bernardo
Carmelilia
C
Felici
Aldo
A
Marrocco
Giacinto
G
Maggiulli
Giorgio
G
Grammatico
Barbara
B
Remotti
Daniele
D
Saccucci
Pietro
P
Valentini
Ferdinando
F
Mazzilli
Maria Cristina
MC
Majore
Silvia
S
Grammatico
Paola
P
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
D012333:RNA, Messenger; D019699:Thrombospondins; C503243:RSPO1 protein, human; D000098907:R-Spondins