Whole exome sequencing identifies homozygous GPR161 mutation in a family with pituitary stalk interruption syndrome

Ender Karaca, Ramazan Buyukkaya, Davut Pehlivan, Wu Lin Charng, Kursat O. Yaykasli, Yavuz Bayram, Tomasz Gambin, Marjorie Withers, Mehmed M. Atik, Ilknur Arslanoglu, Semih Bolu, Serkan Erdin, Ayla Buyukkaya, Emine Yaykasli, Shalini N. Jhangiani, Donna M. Muzny, Richard A. Gibbs, James R. Lupski

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Context: Pituitary stalk interruption syndrome (PSIS) is a rare, congenital anomaly of the pituitary gland characterized by pituitary gland insufficiency, thin or discontinuous pituitary stalk, anterior pituitary hypoplasia, and ectopic positioning of the posterior pituitary gland (neurohypophysis). The clinical presentation of patients with PSIS varies from isolated growthhormone(GH) deficiency to combined pituitary insufficiency and accompanying extrapituitary findings. Mutations in HESX1, LHX4, OTX2, SOX3, and PROKR2 have been associated with PSIS in less than 5% of cases; thus, the underlying genetic etiology for the vast majority of cases remains to be determined. Objective: We applied whole-exome sequencing (WES) to a consanguineous family with two affected siblings who have pituitary gland insufficiency and radiographic findings of hypoplastic (thin) pituitary gland, empty sella, ectopic neurohypophysis, and interrupted pitiutary stalk- characteristic clinical diagnostic findings of PSIS. Design and Participants: WES was applied to two affected and one unaffected siblings. Results: WES of two affected and one unaffected sibling revealed a unique homozygous missense mutation in GPR161, which encodes the orphan G protein-coupled receptor 161, a protein responsible for transducing extracellular signals across the plasma membrane into the cell. Conclusion: Mutations of GPR161 may be implicated as a potential novel cause of PSIS.

Original languageEnglish
Pages (from-to)E140-E147
JournalJournal of Clinical Endocrinology and Metabolism
Issue number1
StatePublished - 1 Jan 2015
Externally publishedYes


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