{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bosticardo M"],"funding":["Michael Smith Foundation for Health Research Health Professional-Investigator Award","DIR, NIAID, NIH","NIDDK NIH HHS","Center for Clinical and Translational Research at Brown University","Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies at St. Louis Children’s Hospital","Center for Cancer Research, National Cancer Institute, National Institutes of Health","NIGMS NIH HHS"],"pagination":["549-561"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6731368"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["105(3)"],"pubmed_abstract":["FOXN1 is the master regulatory gene of thymic epithelium development. FOXN1 deficiency leads to thymic aplasia, alopecia, and nail dystrophy, accounting for the nude/severe combined immunodeficiency (nu/SCID) phenotype in humans and mice. We identified several newborns with low levels of T cell receptor excision circles (TRECs) and T cell lymphopenia at birth, who carried heterozygous loss-of-function FOXN1 variants. Longitudinal analysis showed persistent T cell lymphopenia during infancy, often associated with nail dystrophy. Adult individuals with heterozygous FOXN1 variants had in most cases normal CD4<sup>+</sup> but lower than normal CD8<sup>+</sup> cell counts. We hypothesized a FOXN1 gene dosage effect on the function of thymic epithelial cells (TECs) and thymopoiesis and postulate"],"journal":["American journal of human genetics"],"pubmed_title":["Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis."],"pmcid":["PMC6731368"],"funding_grant_id":["U54 GM115677","GM115677","K08 DK116668"],"pubmed_authors":["Niebur H","Prencipe R","Bhandoola A","Sharapova S","Bosticardo M","Giardino G","Tam JS","Gelfand EW","Biggs C","Kleiner GI","Hill DA","Seroogy CM","Hartog N","Sakovich I","Pignata C","Perez E","Ruffner M","Gebbia J","Cooper MA","Hayward A","Yemialyanava I","Padem N","Butte MJ","Cowan J","Abbott JK","Chen K","Heimall J","Peake J","Scalia G","Corsino C","Notarangelo LD","Yamazaki Y","Seeborg F","Elder ME","Sleasman JW","Crestani E","Bartnikas LM"],"additional_accession":[]},"is_claimable":false,"name":"Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis.","description":"FOXN1 is the master regulatory gene of thymic epithelium development. FOXN1 deficiency leads to thymic aplasia, alopecia, and nail dystrophy, accounting for the nude/severe combined immunodeficiency (nu/SCID) phenotype in humans and mice. We identified several newborns with low levels of T cell receptor excision circles (TRECs) and T cell lymphopenia at birth, who carried heterozygous loss-of-function FOXN1 variants. Longitudinal analysis showed persistent T cell lymphopenia during infancy, often associated with nail dystrophy. Adult individuals with heterozygous FOXN1 variants had in most cases normal CD4<sup>+</sup> but lower than normal CD8<sup>+</sup> cell counts. We hypothesized a FOXN1 gene dosage effect on the function of thymic epithelial cells (TECs) and thymopoiesis and postulate","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Sep","modification":"2026-05-04T18:37:18.046Z","creation":"2020-10-29T08:33:05Z"},"accession":"S-EPMC6731368","cross_references":{"pubmed":["31447097"],"doi":["10.1016/j.ajhg.2019.07.014"]}}