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J Clin Endocrinol Metab. 2015 Jan;100(1):E140-7. doi: 10.1210/jc.2014-1984.

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

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Department of Molecular and Human Genetics (E.K., D.P., W.-L.C., Y.B., T.G., M.W., M.M.A., R.A.G., J.R.L.), Baylor College of Medicine, Houston, Texas 77030; Department of Radiology (R.B.), Duzce University Medical School, 81620 Duzce, Turkey; Department of Medical Biology (K.O.Y.), Kahramanmaras Sutcu Imam University, Medical School, 46100 Kahramanmaras, Turkey; Department of Pediatric Endocrinology (I.A., S.B.), Duzce University Medical School, 81620 Duzce, Turkey; Center for Human Genetic Research (S.E.), Massachussetts General Hospital, Boston, Massachussetts 02114; Department of Radiology (A.B.), Duzce Ataturk Community Hospital, 81620 Duzce, Turkey; Department of Medical Biology and Genetics (E.Y.), Duzce University Institute of Health Science, 81620 Duzce, Turkey; Human Genome Sequencing Center (S.N.J., D.M.M., R.A.G.), Baylor College of Medicine, Houston Texas 77030; Department of Pediatrics (J.R.L.), Baylor College of Medicine, Houston, Texas 77030; and Texas Children's Hospital (J.R.L.), Houston, Texas 77030.



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 growth hormone (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.


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.


WES was applied to two affected and one unaffected siblings.


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.


Mutations of GPR161 may be implicated as a potential novel cause of PSIS.

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