Department of Urology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Department of Genetics and Metabolism, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Asian J Androl. 2022 Jan-Feb;24(1):78-84. doi: 10.4103/aja202175.
Persistent Müllerian duct syndrome (PMDS) is a rare clinically and genetically overlapping disorder caused by mutations in the anti-Müllerian hormone (AMH) gene or the anti-Müllerian hormone receptor type 2 (AMHR2) gene. Affected individuals present uterus and tubes in normally virilized males and are discovered unexpectedly during other surgeries. Since it is rare and complex, a definitive clinical diagnosis can be missed, and there are no guidelines regarding how to deal with the uterus. In the present study, exome sequencing and Sanger verification were performed for causal variants in 12 PMDS patients. Preoperative diagnoses were made by positive exome sequencing in 8 patients. Of them, 7 patients evoked on the basis of ultrasound indicating bilateral testes on the same side of the body. Twelve different AMH variants (2 frameshift/nonsense, 1 deletion, 8 missense, and 1 in-frame) in 9 patients and 6 different AMHR2 variants (5 missense and 1 splicing) in 3 patients were identified. Seven variants were classified as "pathogenic" or "likely pathogenic", and 4 of them were novel. All but two patients with AMH defects showed low serum AMH concentrations, but all patients with AMHR2 defects showed elevated AMH levels. During surgery, an abnormal vas deferens was observed in half of the patients. Eight patients underwent orchidopexy with uterine preservation. Of them, 2 patients presented complications including irreducible cryptorchidism, and 3 patients developed Müllerian remnant cysts. Three patients underwent subtotal hysterectomy. Of them, one patient had complication of injury to the vas deferens, and one had hemorrhage after operation. This is the first report of PMDS involving a large Chinese population. The present study not only expands the variation spectrum but also provides clinical experience about the management of the uterus.
持续性 Müllerian 管发育不全综合征（PMDS）是一种罕见的临床和遗传上相互重叠的疾病，由抗 Müllerian 激素（AMH）基因或抗 Müllerian 激素受体 2 型（AMHR2）基因突变引起。受影响的个体在正常男性中表现为子宫和输卵管，并在其他手术中意外发现。由于其罕见且复杂，可能会错过明确的临床诊断，并且对于如何处理子宫也没有指导方针。在本研究中，对 12 名 PMDS 患者进行了外显子组测序和 Sanger 验证，以确定病因变异。8 名患者通过阳性外显子组测序做出术前诊断。其中，7 名患者的超声检查结果为同侧双侧睾丸，提示为该病。在 9 名患者中发现了 12 种不同的 AMH 变异（2 种移码/无义，1 种缺失，8 种错义，1 种框内），在 3 名患者中发现了 6 种不同的 AMHR2 变异（5 种错义，1 种剪接）。7 种变异被归类为“致病性”或“可能致病性”，其中 4 种为新变异。所有 AMH 缺陷患者的血清 AMH 浓度均较低，但所有 AMHR2 缺陷患者的 AMH 水平均升高。手术过程中，一半患者的异常输精管被观察到。8 名患者行保留子宫的睾丸固定术。其中，2 名患者出现并发症，包括不可还原的隐睾，3 名患者出现 Müllerian 残余囊肿。3 名患者行次全子宫切除术。其中，1 名患者发生输精管损伤并发症，1 名患者术后出血。这是首次报道涉及中国人群的 PMDS。本研究不仅扩大了变异谱，还提供了关于子宫管理的临床经验。
