title: Complete sex reversal in a WAGR syndrome patient.
abstract: The WAGR contiguous gene deletion syndrome is a combination of Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation. Children with WAGR syndrome invariably have a constitutional chromosomal deletion at 11p13. WT1 haploinsufficiency is associated with a significant risk of Wilms tumor while PAX6 haploinsufficiency lead to aniridia, both genes located in the deleted region. The 46,XY patients with WAGR syndrome are often born with genital abnormalities such as cryptorchidism or hypospadias but more rarely ambiguous genitalia. To our knowledge, complete sex reversal has never been observed in WAGR syndrome patients. Here, we report on the clinical, cytogenetic, and molecular characterization of a child with WAGR syndrome and complete sex reversal. The young girl had female external and internal genitalia with normal uterus and fallopian tubes while the ovaries were not observed. Chromosomal analysis showed a 46,XY,del(11)(p12p14.1) karyotype. A 1-Mb resolution array CGH experiment estimated the size of the interstitial deletion at approximately 10 Mb encompassing WT1 and PAX6. The entire coding regions of WT1 and SRY have been sequenced and no mutation has been identified. Frasier syndrome (FS) and Denys-Drash syndrome (DDS) are two disorders associated with mutations in the WT1 gene. Complete sex reversal is a feature usually present in FS and sometimes in DDS, but until now never observed in WAGR syndrome. The present report suggests that these conditions may be considered as part of the spectrum of disease due to WT1 gene alterations.
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire, Nantes, France. cedric.lecaignec@chu-nantes.fr
authors.forename: Cedric
authors.initials: C
authors.lastname: Le Caignec
authors.forename: Capucine
authors.initials: C
authors.lastname: Delnatte
authors.forename: Joris R
authors.initials: JR
authors.lastname: Vermeesch
authors.forename: Michelle
authors.initials: M
authors.lastname: Boceno
authors.forename: Madeleine
authors.initials: M
authors.lastname: Joubert
authors.forename: Francoise
authors.initials: F
authors.lastname: Lavenant
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Rival
mesh_terms: D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D020732:Cytogenetic Analysis; D012734:Disorders of Sex Development; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D017624:WAGR Syndrome; D025721:WT1 Proteins / Q000235:genetics
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D025721:WT1 Proteins