Open AccessMulti‐genic pattern found in rare type of hypopituitarism: a whole‐exome sequencing study of Han Chinese with pituitary stalk interruption syndrome
Author(s) -
Guo QingHua,
Wang ChengZhi,
Wu ZhiQiang,
Qin Yan,
Han BaiYu,
Wang AnPing,
Wang BaoAn,
Dou JingTao,
Wu XiaoSheng,
Mu YiMing
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13272
Subject(s) - hypopituitarism , exome sequencing , exome , biology , genetics , mutation , wnt signaling pathway , genetic heterogeneity , bioinformatics , gene , phenotype , endocrinology
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 .