Multi‐genic pattern found in rare type of hypopituitarism: a whole‐exome sequencing study of Han Chinese with pituitary stalk interruption syndrome |
| |
| Authors: | Zhi‐Qiang Wu Yan Qin Bai‐Yu Han An‐Ping Wang Bao‐An Wang Jing‐Tao Dou Xiao‐Sheng Wu Yi‐Ming Mu |
| |
| Institution: | 1. Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, China;2. Department of Endocrinology, The First Affiliated Hospital of Xinxiang Medical University, Weihui City, Henan, China;3. Department of Endocrinology, Chinese PLA General Hospital, Beijing, China;4. Department of Endocrinology and Metabolism, The 264 Hospital of PLA, Taiyuan, Shanxi, China;5. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA;6. Department of Immunology, Mayo Clinic, Rochester, MN, USA |
| |
| Abstract: | 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. |
| |
| Keywords: | pituitary stalk interruption syndrome whole‐exome sequencing pathogenesis pathway bioinformatics |
|
|
