{"PubmedArticle":{"MedlineCitation":{"@attributes":{"Status":"MEDLINE","Owner":"NLM","IndexingMethod":"Manual"},"PMID":{"@attributes":{"Version":"1"},"@text":"25192046"},"DateCompleted":{"Year":"2014","Month":"10","Day":"30"},"DateRevised":{"Year":"2025","Month":"05","Day":"29"},"Article":{"@attributes":{"PubModel":"Print"},"Journal":{"ISSN":{"@attributes":{"IssnType":"Electronic"},"@text":"1537-6605"},"JournalIssue":{"@attributes":{"CitedMedium":"Internet"},"Volume":"95","Issue":"3","PubDate":{"Year":"2014","Month":"Sep","Day":"04"}},"Title":"American journal of human genetics","ISOAbbreviation":"Am J Hum Genet"},"ArticleTitle":"Mutations in FEZF1 cause Kallmann syndrome.","Pagination":{"StartPage":"326","EndPage":"331","MedlinePgn":"326-31"},"ELocationID":[{"@attributes":{"EIdType":"doi","ValidYN":"Y"},"@text":"10.1016\/j.ajhg.2014.08.006"},{"@attributes":{"EIdType":"pii","ValidYN":"Y"},"@text":"S0002-9297(14)00350-4"}],"Abstract":{"AbstractText":["Gonadotropin-releasing hormone (GnRH) neurons originate outside the CNS in the olfactory placode and migrate into the CNS, where they become integral components of the hypothalamic-pituitary-gonadal (HPG) axis. Disruption of this migration results in Kallmann syndrome (KS), which is characterized by anosmia and pubertal failure due to hypogonadotropic hypogonadism. Using candidate-gene screening, autozygosity mapping, and whole-exome sequencing in a cohort of 30 individuals with KS, we searched for genes newly associated with KS. We identified homozygous loss-of-function mutations in FEZF1 in two independent consanguineous families each with two affected siblings. The FEZF1 product is known to enable axons of olfactory receptor neurons (ORNs) to penetrate the CNS basal lamina in mice. Because a subset of axons in these tracks is the migratory pathway for GnRH neurons, in FEZF1 deficiency, GnRH neurons also fail to enter the brain. These results indicate that FEZF1 is required for establishment of the central component of the HPG axis in humans."],"CopyrightInformation":"Copyright \u00a9 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved."},"AuthorList":{"@attributes":{"CompleteYN":"Y"},"Author":[{"@attributes":{"ValidYN":"Y"},"LastName":"Kotan","ForeName":"L Damla","Initials":"LD","AffiliationInfo":[{"Affiliation":"Department of Biotechnology, Institute of Sciences, Cukurova University, 01330 Adana, Turkey."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Hutchins","ForeName":"B Ian","Initials":"BI","AffiliationInfo":[{"Affiliation":"Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Ozkan","ForeName":"Yusuf","Initials":"Y","AffiliationInfo":[{"Affiliation":"Department of Endocrinology, Faculty of Medicine, F\u0131rat University, 23119 Elaz\u0131g, Turkey."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Demirel","ForeName":"Fatma","Initials":"F","AffiliationInfo":[{"Affiliation":"Division of Pediatric Endocrinology, Ankara Pediatric Hematology and Oncology Training Hospital, 06200 Ankara, Turkey."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Stoner","ForeName":"Hudson","Initials":"H","AffiliationInfo":[{"Affiliation":"Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Cheng","ForeName":"Paul J","Initials":"PJ","AffiliationInfo":[{"Affiliation":"Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Esen","ForeName":"Ihsan","Initials":"I","AffiliationInfo":[{"Affiliation":"Division of Pediatric Endocrinology, Ankara Pediatric Hematology and Oncology Training Hospital, 06200 Ankara, Turkey."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Gurbuz","ForeName":"Fatih","Initials":"F","AffiliationInfo":[{"Affiliation":"Division of Pediatric Endocrinology, Faculty of Medicine, Cukurova University, 01330 Adana, Turkey."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Bicakci","ForeName":"Y Kenan","Initials":"YK","AffiliationInfo":[{"Affiliation":"Department of Radiology, Faculty of Medicine, Cukurova University, 01330 Adana, Turkey."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Mengen","ForeName":"Eda","Initials":"E","AffiliationInfo":[{"Affiliation":"Division of Pediatric Endocrinology, Faculty of Medicine, Cukurova University, 01330 Adana, Turkey."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Yuksel","ForeName":"Bilgin","Initials":"B","AffiliationInfo":[{"Affiliation":"Division of Pediatric Endocrinology, Faculty of Medicine, Cukurova University, 01330 Adana, Turkey."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Wray","ForeName":"Susan","Initials":"S","AffiliationInfo":[{"Affiliation":"Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA. Electronic address: wrays@ninds.nih.gov."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Topaloglu","ForeName":"A Kemal","Initials":"AK","AffiliationInfo":[{"Affiliation":"Department of Biotechnology, Institute of Sciences, Cukurova University, 01330 Adana, Turkey; Division of Pediatric Endocrinology, Faculty of Medicine, Cukurova University, 01330 Adana, Turkey. Electronic address: ktopaloglu@cu.edu.tr."}]}]},"Language":["eng"],"GrantList":{"@attributes":{"CompleteYN":"Y"},"Grant":[{"GrantID":"Z01 NS002824","Acronym":"ImNIH","Agency":"Intramural NIH HHS","Country":"United States"},{"GrantID":"NS002824-13","Acronym":"NS","Agency":"NINDS NIH HHS","Country":"United States"}]},"PublicationTypeList":{"PublicationType":[{"@attributes":{"UI":"D016428"},"@text":"Journal Article"},{"@attributes":{"UI":"D016448"},"@text":"Multicenter Study"},{"@attributes":{"UI":"D052061"},"@text":"Research Support, N.I.H., Extramural"},{"@attributes":{"UI":"D013485"},"@text":"Research Support, Non-U.S. Gov't"}]}},"MedlineJournalInfo":{"Country":"United States","MedlineTA":"Am J Hum Genet","NlmUniqueID":"0370475","ISSNLinking":"0002-9297"},"ChemicalList":{"Chemical":[{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D004268"},"@text":"DNA-Binding Proteins"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C557090"},"@text":"FEZF2 protein, human"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C560820"},"@text":"Fezf1 protein, mouse"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D009419"},"@text":"Nerve Tissue Proteins"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D012097"},"@text":"Repressor Proteins"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D014157"},"@text":"Transcription Factors"}},{"RegistryNumber":"33515-09-2","NameOfSubstance":{"@attributes":{"UI":"D007987"},"@text":"Gonadotropin-Releasing Hormone"}}]},"CitationSubset":["IM"],"MeshHeadingList":{"MeshHeading":[{"DescriptorName":{"@attributes":{"UI":"D000293","MajorTopicYN":"N"},"@text":"Adolescent"}},{"DescriptorName":{"@attributes":{"UI":"D000328","MajorTopicYN":"N"},"@text":"Adult"}},{"DescriptorName":{"@attributes":{"UI":"D000818","MajorTopicYN":"N"},"@text":"Animals"}},{"DescriptorName":{"@attributes":{"UI":"D001369","MajorTopicYN":"N"},"@text":"Axons"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"},{"@attributes":{"UI":"Q000473","MajorTopicYN":"N"},"@text":"pathology"}]},{"DescriptorName":{"@attributes":{"UI":"D001921","MajorTopicYN":"N"},"@text":"Brain"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"},{"@attributes":{"UI":"Q000473","MajorTopicYN":"N"},"@text":"pathology"}]},{"DescriptorName":{"@attributes":{"UI":"D002648","MajorTopicYN":"N"},"@text":"Child"}},{"DescriptorName":{"@attributes":{"UI":"D004268","MajorTopicYN":"N"},"@text":"DNA-Binding Proteins"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"Y"},"@text":"genetics"}]},{"DescriptorName":{"@attributes":{"UI":"D005190","MajorTopicYN":"N"},"@text":"Family"}},{"DescriptorName":{"@attributes":{"UI":"D005260","MajorTopicYN":"N"},"@text":"Female"}},{"DescriptorName":{"@attributes":{"UI":"D007987","MajorTopicYN":"N"},"@text":"Gonadotropin-Releasing Hormone"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D006801","MajorTopicYN":"N"},"@text":"Humans"}},{"DescriptorName":{"@attributes":{"UI":"D007006","MajorTopicYN":"N"},"@text":"Hypogonadism"}},{"DescriptorName":{"@attributes":{"UI":"D007030","MajorTopicYN":"N"},"@text":"Hypothalamo-Hypophyseal System"}},{"DescriptorName":{"@attributes":{"UI":"D017436","MajorTopicYN":"N"},"@text":"Kallmann Syndrome"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"Y"},"@text":"genetics"}]},{"DescriptorName":{"@attributes":{"UI":"D008297","MajorTopicYN":"N"},"@text":"Male"}},{"DescriptorName":{"@attributes":{"UI":"D051379","MajorTopicYN":"N"},"@text":"Mice"}},{"DescriptorName":{"@attributes":{"UI":"D009154","MajorTopicYN":"N"},"@text":"Mutation"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"Y"},"@text":"genetics"}]},{"DescriptorName":{"@attributes":{"UI":"D009419","MajorTopicYN":"N"},"@text":"Nerve Tissue Proteins"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"Y"},"@text":"genetics"}]},{"DescriptorName":{"@attributes":{"UI":"D018034","MajorTopicYN":"N"},"@text":"Olfactory Receptor Neurons"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"},{"@attributes":{"UI":"Q000473","MajorTopicYN":"N"},"@text":"pathology"}]},{"DescriptorName":{"@attributes":{"UI":"D010375","MajorTopicYN":"N"},"@text":"Pedigree"}},{"DescriptorName":{"@attributes":{"UI":"D011446","MajorTopicYN":"N"},"@text":"Prospective Studies"}},{"DescriptorName":{"@attributes":{"UI":"D012097","MajorTopicYN":"N"},"@text":"Repressor Proteins"}},{"DescriptorName":{"@attributes":{"UI":"D014157","MajorTopicYN":"N"},"@text":"Transcription Factors"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"Y"},"@text":"genetics"}]},{"DescriptorName":{"@attributes":{"UI":"D055815","MajorTopicYN":"N"},"@text":"Young Adult"}}]}},"PubmedData":{"History":{"PubMedPubDate":[{"@attributes":{"PubStatus":"received"},"Year":"2014","Month":"7","Day":"16"},{"@attributes":{"PubStatus":"accepted"},"Year":"2014","Month":"8","Day":"14"},{"@attributes":{"PubStatus":"entrez"},"Year":"2014","Month":"9","Day":"6","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"pubmed"},"Year":"2014","Month":"9","Day":"6","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"medline"},"Year":"2014","Month":"10","Day":"31","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"pmc-release"},"Year":"2015","Month":"3","Day":"4"}]},"PublicationStatus":"ppublish","ArticleIdList":{"ArticleId":[{"@attributes":{"IdType":"pubmed"},"@text":"25192046"},{"@attributes":{"IdType":"pmc"},"@text":"PMC4157145"},{"@attributes":{"IdType":"doi"},"@text":"10.1016\/j.ajhg.2014.08.006"},{"@attributes":{"IdType":"pii"},"@text":"S0002-9297(14)00350-4"}]},"ReferenceList":[{"Reference":[{"Citation":"Schwanzel-Fukuda M., Pfaff D.W. 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