Service d'Hormonologie, Hôpital Lapeyronie, Centre Hospitalier Universitaire (CHU) Montpellier and Université Montpellier I, 34295 Montpellier, France.
J Clin Endocrinol Metab. 2011 Feb;96(2):296-307. doi: 10.1210/jc.2010-1024. Epub 2010 Dec 8.
In 46,XY disorders of sex development, 5α-reductase deficiency is rare and is not usually the first-intention diagnosis in newborn ambiguous genitalia, contrary to partial androgen insensitivity syndrome. Yet the cause of ambiguous genitalia may guide sex assignment, and rapid, precise diagnosis of 5α-reductase deficiency is essential.
The aim of the study was to describe relevant data for clinical diagnosis, biological investigation, and molecular determination from 55 patients with srd5A2 mutations identified in our laboratory over 20 yr to improve early diagnosis.
The study was performed at Montpellier University Hospital.
We studied a cohort of 55 patients with srd5A2 gene mutations.
MAIN OUTCOME MEASURE(S): Genetic analysis of srd5A2 was conducted.
Clitoromegaly (49.1%) and microphallus with various degrees of hypospadias (32.7%) were frequent phenotypes. Female external genitalia (7.3%) and isolated micropenis (3.6%) were rare. Seventy-two percent of patients were initially assigned to female gender; five of them (12.5%) switched to male sex in peripuberty. Over 72% of patients were considered for 5α-reductase deficiency diagnosis when the testosterone/dihydrotestosterone cutoff was 10. In 55 patients (with 20 having a history of consanguinity), we identified 33 different mutations. Five have never been reported: p.G32S, p.Y91H, p.G104E, p.F223S, and c.461delT. Homozygous mutations were present in 69.1% of cases, compound heterozygous mutations in 25.5%, and compound heterozygous mutations alone with the V89L polymorphism in 5.4%. Exons 1 and 4 were most affected, with 35.8 and 21.7% mutant alleles per exon, respectively.
In the largest cohort to date, we demonstrate a wide spectrum of phenotypes and biological profiles in patients with 5α-reductase deficiency, whatever their geographical or ethnic origins.
在 46，XY 性发育障碍中，5α-还原酶缺乏症很少见，通常不是新生儿外生殖器模糊的首选诊断，与部分雄激素不敏感综合征相反。然而，外生殖器的病因可能会指导性别分配，快速、准确地诊断 5α-还原酶缺乏症至关重要。
本研究旨在描述我们实验室在 20 年中发现的 55 例 srd5A2 基因突变患者的临床诊断、生物学研究和分子学检测的相关数据，以提高早期诊断水平。
研究在蒙彼利埃大学医院进行。
我们研究了一组 55 例 srd5A2 基因突变患者。
进行 srd5A2 基因的遗传分析。
阴蒂肥大（49.1%）和不同程度尿道下裂的小阴茎（32.7%）是常见的表型。女性外生殖器（7.3%）和孤立性小阴茎（3.6%）罕见。72%的患者最初被分配为女性性别；其中 5 例（12.5%）在青春期转为男性。当睾酮/双氢睾酮的截断值为 10 时，超过 72%的患者被认为患有 5α-还原酶缺乏症。在 55 例患者（其中 20 例有近亲结婚史）中，我们发现了 33 种不同的突变。有 5 种从未报道过：p.G32S、p.Y91H、p.G104E、p.F223S 和 c.461delT。69.1%的病例为纯合突变，25.5%为复合杂合突变，5.4%为复合杂合突变合并 V89L 多态性。受影响最严重的外显子是 1 和 4，每个外显子的突变等位基因分别为 35.8%和 21.7%。
在迄今为止最大的队列中，我们证明了无论其地理位置或种族来源如何，5α-还原酶缺乏症患者的表型和生物学特征都呈现广泛的谱。
