Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
Department of Endocrinology, Hainan Branch of Chinese PLA General Hospital, Sanya, Hainan, China.
J Cell Mol Med. 2017 Dec;21(12):3626-3632. doi: 10.1111/jcmm.13272. Epub 2017 Jul 14.
Pituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole-exome sequencing (WES) and bioinformatic analysis. We identified a group of heterozygous mutations in 92% (22 of 24) of the patients, and these genes are mostly associated with Notch, Shh, Wnt signalling pathways. Importantly, 83% (20 of 24) of the patients had more than one mutation in those pathways suggesting synergy of compound mutations underpin the pathogenesis of sporadic PSIS.
垂体柄中断综合征（PSIS）是一种罕见的垂体功能减退症，表现为不同程度的垂体激素缺乏。虽然在一些家族性病例中已经发现了突变，但绝大多数散发性 PSIS 患者的潜在机制仍难以捉摸，需要使用系统方法进行全面研究。我们假设其他遗传机制可能与散发性 PSIS 有关。为了验证这一假说，我们使用全外显子组测序（WES）和生物信息学分析对 24 名无家族史的汉族 PSIS 患者进行了研究。我们在 92%（22/24）的患者中发现了一组杂合突变，这些基因主要与 Notch、Shh、Wnt 信号通路有关。重要的是，83%（20/24）的患者在这些通路中存在不止一种突变，这表明复合突变的协同作用是散发性 PSIS 发病机制的基础。
