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Abstract：
A novel CYP11A1: c.1236 + 5G > A was identified, expanding the mutation spectrum of the congenital adrenal insufficiency with 46,XY sex reversal. In a now 17-year-old girl delivered full-term (G2P2, parents unrelated), adrenal failure was diagnosed in the first year of life based on clinical picture of acute adrenal crisis with vomiting, dehydration, weight loss, hypotension, and electrolyte disturbances. At the time, hormonal tests revealed primary adrenocortical insufficiency and steroid profiles showed lack of products of steroidogenesis, and since then the patient has been treated with substitution doses of hydrocortisone and fludrocortisone. At the age of 14, considering the absence of puberty symptoms, extended diagnostic tests revealed elevated LH levels (26.5 mIU/mL) with pre-puberty FSH levels (4.9 mIU/mL), low estradiol (28 pmol/L), testosterone (<2.5 ng/mL), and extremely high levels of ACTH (4961 pg/mL). A cytogenetic study revealed a 46 XY karyotype. A molecular examination confirmed the missense mutation and a novel splice-site mutation of CYP11A1 gene. Compound heterozygosity for the CYP11A1 gene with a known pathogenic variant in one allele and a novel splice site mutation in the second allele is most probably responsible for congenital adrenal insufficiency with 46,XY sex reversal. We discuss the necessity of cytogenetic test in the case of early onset of adrenal failure in the absence of steroidogenesis metabolites in the steroid profile.
摘要：
一个新的CYP11A1：c.1236+5G>A被鉴定，用46，XY性别逆转扩大先天性肾上腺功能不全的突变谱。在一个现在17岁的女孩中，足月分娩（G2P2，父母无关），根据急性肾上腺危象伴呕吐的临床表现，在生命的第一年诊断为肾上腺衰竭，脱水,减肥,低血压,和电解质干扰。当时,激素测试显示原发性肾上腺皮质功能不全和类固醇谱显示缺乏类固醇生成的产物，此后，患者接受了替代剂量的氢化可的松和氟氢可的松治疗。在14岁时，考虑到没有青春期症状，延长诊断测试显示LH水平升高（26.5mIU/mL）与青春期前FSH水平（4.9mIU/mL），低雌二醇（28pmol/L），睾酮（<2.5ng/mL），和极高水平的ACTH（4961pg/mL）。细胞遗传学研究显示46XY核型。分子检查证实了CYP11A1基因的错义突变和新的剪接位点突变。CYP11A1基因的复合杂合性在一个等位基因中具有已知的致病性变异，在第二个等位基因中具有新的剪接位点突变，这很可能是先天性肾上腺功能不全的46，XY性别逆转的原因。我们讨论了在类固醇中缺乏类固醇生成代谢物的情况下，在肾上腺衰竭早期发作的情况下进行细胞遗传学测试的必要性。
