Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Department of Molecular Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Endocr Pract. 2014 Oct;20(10):e191-7. doi: 10.4158/EP14179.CR.
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.
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.
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.
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.
描述 3 位患有先天性肾上腺皮质增生症（CAH）的女性核型姐妹，她们因 CYP11B1 基因突变而表现出冲突的性别认同，出生时被指定为男性，并随访至成年。
我们介绍了 3 位姐妹（16、14 和 10 岁），她们出生时生殖器严重男性化，被抚养为男性。临床检查显示外阴生殖器为 Prader IV 至 V 级，阴茎伸展长度为 7 至 11 厘米。促肾上腺皮质激素（ACTH）刺激试验显示，11 去氧皮质醇（11DOC）水平受刺激后为 12300-18700μg/L（正常值 0-5μg/L）。她们的核型均为 46XX，盆腔超声显示子宫和卵巢大小正常。从外周白细胞中提取 DNA，聚合酶链反应（PCR）和直接测序显示 CYP11B1 存在新的突变。该突变导致 c.53_54T 插入（c.53_54insT），引起 CYP11B1 第 115 位（密码子 39）的移码和截断。
对年龄最大的姐妹进行心理评估提示其性别认同为女性，经过 1 年的社会心理调整后，她宣布自己为女性并进行了性别重置。对另外 2 位年龄较小的姐妹和第 4 位具有相同情况的 46XY 兄弟进行心理评估显示其性别认同为男性，他们在没有明显困难的情况下继续以男性身份生活。
3 位患有严重男性化 CAH 的 46XX 姐妹携带相同的 CYP11B1 突变，具有相似的产后且可能是产前雄激素暴露和环境情况，但表现出不同的性别认同。这些病例表明，性别认同的基础比染色体、生化和遗传构成更为复杂。
