Whole-Exome Sequencing Identifies Homozygous GPR161 Mutation in a Family with Pituitary Stalk Interruption Syndrome

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 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. 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 a...