title: Divergent gender identity in three siblings with 46XX karyotype and severely virilizing congenital adrenal hyperplasia caused by a novel CYP11B1 mutation.
abstract: OBJECTIVE
  To describe conflicting gender identities in three karyotypically female siblings with congenital adrenal hyperplasia (CAH) caused by a novel mutation in the CYP11B1 gene, who were assigned as males at birth and followed up to adulthood.
  
  
  METHODS
  We present 3 siblings (16, 14 and 10 years old) who were born with severe genital virilization and raised as males. Clinical examination showed Prader IV to V external genitalia with a stretched penile length of 7 to 11 cm. Adrenocorticotrophic hormone (ACTH) stimulation test showed a stimulated 11 deoxycortisol (11DOC) level of 12,300-18,700 μg/L (normal 0-5 μg/L). Their karyotypes were 46 XX, and they had normal-sized uterus and ovaries on pelvic ultrasound. DNA was isolated from peripheral leukocytes, and polymerase chain reaction (PCR) and direct sequencing revealed a novel CYP11B1 mutation. This mutation leads to a c.53_54 T insertion (c.53_54insT) with frameshift and truncation at c.115 (codon 39) of CYP11B1.
  
  
  RESULTS
  Psychological evaluation of the oldest sibling suggested a female gender identity, and she declared herself as female, and female sex was re-assigned after 1 year of psychosocial adjustment. Psychological assessment for the 2 younger siblings and a fourth 46XY sibling with the same condition revealed male gender identities, and they continued their lives as males without significant difficulties.
  
  
  CONCLUSIONS
  Divergent gender identity was observed in three severely masculinized 46XX siblings with CAH who carried the same CYP11B1 mutation and had comparable postnatal and probably prenatal androgen exposure and environmental circumstances. These cases suggest that the basis of gender identity is more complex than chromosomal, biochemical, and genetic constitution.
authors.affiliation: Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Bassam
authors.initials: B
authors.lastname: Bin-Abbas
authors.affiliation: Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Doha
authors.initials: D
authors.lastname: Al-Humaida
authors.affiliation: Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Afaf
authors.initials: A
authors.lastname: Al-Sagheir
authors.affiliation: Department of Molecular Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Ebtesam
authors.initials: E
authors.lastname: Qasem
authors.affiliation: Department of Molecular Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Mai
authors.initials: M
authors.lastname: Almohanna
authors.affiliation: Department of Molecular Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Alzahrani
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital; D002648:Child; D005260:Female; D005783:Gender Identity; D006801:Humans; D059785:Karyotype; D008297:Male; D009154:Mutation; D035781:Siblings; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics*
chemical_list: D013252:Steroid 11-beta-Hydroxylase