title: Nijmegen breakage syndrome detected by newborn screening for T cell receptor excision circles (TRECs).
abstract: OBJECTIVE
  Severe combined immunodeficiency (SCID) encompasses a group of disorders characterized by reduced or absent T-cell number and function and identified by newborn screening utilizing T-cell receptor excision circles (TRECs). This screening has also identified infants with T lymphopenia who lack mutations in typical SCID genes. We report an infant with low TRECs and non-SCID T lymphopenia, who proved upon whole exome sequencing to have Nijmegen breakage syndrome (NBS).
  
  
  METHODS
  Exome sequencing of DNA from the infant and his parents was performed. Genomic analysis revealed deleterious variants in the NBN gene. Confirmatory testing included Sanger sequencing and immunoblotting and radiosensitivity testing of patient lymphocytes.
  
  
  RESULTS
  Two novel nonsense mutations in NBN were identified in genomic DNA from the family. Immunoblotting showed absence of nibrin protein. A colony survival assay demonstrated radiosensitivity comparable to patients with ataxia telangiectasia.
  
  
  CONCLUSIONS
  Although TREC screening was developed to identify newborns with SCID, it has also identified T lymphopenic disorders that may not otherwise be diagnosed until later in life. Timely identification of an infant with T lymphopenia allowed for prompt pursuit of underlying etiology, making possible a diagnosis of NBS, genetic counseling, and early intervention to minimize complications.
authors: Division of General Pediatrics, Children's Hospital of Los Angeles, Los Angeles, CA, USA, jpatel@chla.usc.edu.
authors: Jay P
authors: JP
authors: Patel
authors: Jennifer M
authors: JM
authors: Puck
authors: Rajgopal
authors: R
authors: Srinivasan
authors: Christina
authors: C
authors: Brown
authors: Uma
authors: U
authors: Sunderam
authors: Kunal
authors: K
authors: Kundu
authors: Steven E
authors: SE
authors: Brenner
authors: Richard A
authors: RA
authors: Gatti
authors: Joseph A
authors: JA
authors: Church
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004270:DNA, Circular; D059472:Exome; D015329:Gene Rearrangement, T-Lymphocyte; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D049932:Nijmegen Breakage Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004270:DNA, Circular; C112156:NBN protein, human; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell