细胞色素P450氧化还原酶基因新突变导致的46,XX性发育障碍和安特利-比克斯勒综合征

46,XX DSD and Antley-Bixler syndrome due to novel mutations in the cytochrome P450 oxidoreductase gene.

作者信息

Guaragna-Filho Guilherme, Castro Carla Cristina Telles de Sousa, Carvalho Rodrigo Ribeiro De, Coeli Fernanda Borchers, Ferraz Lúcio Fábio Caldas, Petroli Reginaldo José, Mello Maricilda Palandi De, Sewaybricker Letícia Esposito, Lemos-Marini Sofia Helena Valente, D'Souza-Li Lilia Freire Rodrigues, Miranda Márcio Lopes, Maciel-Guerra Andréa Trevas, Guerra-Junior Gil

机构信息

Departamento de Pediatria, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil.

出版信息

Arq Bras Endocrinol Metabol. 2012 Nov;56(8):578-85. doi: 10.1590/s0004-27302012000800020.

DOI:10.1590/s0004-27302012000800020

PMID:23295302

Abstract

Deficiency of the enzyme P450 oxidoreductase is a rare form of congenital adrenal hyperplasia with characteristics of combined and partial impairments in steroidogenic enzyme activities, as P450 oxidoreductase transfers electrons to CYP21A2, CYP17A1, and CYP19A1. It results in disorders of sex development and skeletal malformations similar to Antley-Bixley syndrome. We report the case of a 9-year-old girl who was born with virilized genitalia (Prader stage V), absence of palpable gonads, 46,XX karyotype, and hypergonadotropic hypogonadism. During the first year of life, ovarian cyst, partial adrenal insufficiency, and osteoarticular changes, such as mild craniosynostosis, carpal and tarsal synostosis, and limited forearm pronosupination were observed. Her mother presented severe virilization during pregnancy. The molecular analysis of P450 oxidoreductase gene revealed compound heterozygosis for the nonsense p.Arg223*, and the novel missense p.Met408Lys, inherited from the father and the mother, respectively.

摘要

细胞色素P450氧化还原酶缺乏症是先天性肾上腺皮质增生症的一种罕见形式，其特征是类固醇生成酶活性存在联合性和部分性损害，因为细胞色素P450氧化还原酶将电子传递给CYP21A2、CYP17A1和CYP19A1。它会导致性发育障碍和骨骼畸形，类似于安特利-比克斯利综合征。我们报告了一名9岁女孩的病例，她出生时生殖器男性化（普拉德V期），未触及性腺，核型为46,XX，以及高促性腺激素性性腺功能减退。在生命的第一年，观察到卵巢囊肿、部分肾上腺功能不全以及骨关节变化，如轻度颅骨缝早闭、腕骨和跗骨融合以及前臂旋前旋后受限。她的母亲在怀孕期间出现了严重的男性化。细胞色素P450氧化还原酶基因的分子分析显示，分别从父亲和母亲遗传而来的无义突变p.Arg223*和新的错义突变p.Met408Lys的复合杂合性。