title: Is IGSF1 involved in human pituitary tumor formation?
abstract: IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary. Pathogenic mutations in the IGSF1 gene (on Xq26.2) are associated with X-linked central hypothyroidism and testicular enlargement in males. In this study, we tested the hypothesis that IGSF1 is involved in the development of pituitary tumors, especially those that produce growth hormone (GH). IGSF1 was sequenced in 21 patients with gigantism or acromegaly and 92 healthy individuals. Expression studies with a candidate pathogenic IGSF1 variant were carried out in transfected cells and immunohistochemistry for IGSF1 was performed in the sections of GH-producing adenomas, familial somatomammotroph hyperplasia, and in normal pituitary. We identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function, in two male patients and one female with somatomammotroph hyperplasia from the same family. Of 60 female controls, two carried the same variant and seven were heterozygous for other variants. Immunohistochemistry showed increased IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p.N604T variant compared with a GH-producing adenoma from a patient negative for any IGSF1 variants and with normal control pituitary tissue. The IGSF1 gene appears polymorphic in the general population. A potentially pathogenic variant identified in the germline of three patients with gigantism from the same family (segregating with the disease) was also detected in two healthy female controls. Variations in IGSF1 expression in pituitary tissue in patients with or without IGSF1 germline mutations point to the need for further studies of IGSF1 action in pituitary adenoma formation.
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric 
authors.forename: Fabio R
authors.initials: FR
authors.lastname: Faucz
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Anelia D
authors.initials: AD
authors.lastname: Horvath
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Monalisa F
authors.initials: MF
authors.lastname: Azevedo
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Isaac
authors.initials: I
authors.lastname: Levy
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Beata
authors.initials: B
authors.lastname: Bak
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Xekouki
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Eva
authors.initials: E
authors.lastname: Szarek
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric 
authors.forename: Evgenia
authors.initials: E
authors.lastname: Gourgari
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Allison D
authors.initials: AD
authors.lastname: Manning
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric 
authors.forename: Rodrigo Bertollo
authors.initials: RB
authors.lastname: de Alexandre
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Saloustros
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Trivellin
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Maya
authors.initials: M
authors.lastname: Lodish
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric 
authors.forename: Yvonne C
authors.initials: YC
authors.lastname: Anderson
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Ian
authors.initials: I
authors.lastname: Holdaway
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Edward
authors.initials: E
authors.lastname: Oldfield
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Prashant
authors.initials: P
authors.lastname: Chittiboina
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Nesterova
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Nienke R
authors.initials: NR
authors.lastname: Biermasz
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Bernard
authors.affiliation: Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric Endocrinology Inter-institute Training ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USAThe Liggins InstituteUniversity of Auckland, Auckland 1023, New ZealandTaranaki Base HospitalNew Plymouth 4310, New ZealandAuckland City Hospital & Greenlane Clinical CentreAuckland 1142, New ZealandDepartment of NeurosurgeryUniversity of Virginia Health Sciences Center, University of Virginia, Charlottesville, Virginia 22904, USASurgical Neurology BranchNational Institute for Neurological Diseases and Stroke (NINDS), National Institutes of Health, Bethesda, Maryland 20892, USA Departments ofEndocrinology and Metabolic DisordersPediatricsLeiden University Medical Center, Leiden 2333, The Netherlands Section on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, NIH-Clinical Research Center, 10 Center Drive, Building 10, Room 1-3330, MSC1103, Bethesda, Maryland 20892, USAGroup for Advanced Molecular InvestigationGraduate Program in Health Science, Medical School, Pontificia Universidade Catolica do Paraná, Curitiba 80215, BrazilDepartment of Pharmacology and TherapeuticsMcGill University, Montréal, Québec, Canada H3G 1Y6Pediatric 
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000172:Acromegaly / Q000235:genetics; D000818:Animals; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D018095:Germ-Line Mutation; D005877:Gigantism / Q000235:genetics; D057809:HEK293 Cells; D019382:Human Growth Hormone / Q000096:biosynthesis*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008958:Models, Molecular; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D014162:Transfection
chemical_list: C112314:IGSF1 protein, human; D007136:Immunoglobulins; D008565:Membrane Proteins; D019382:Human Growth Hormone
keywords: IGSF1; acromegaly; gigantism; growth hormone; overgrowth; pituitary tumor