title: Variants in TNIP1, a regulator of the NF-kB pathway, found in two patients with neural tube defects.
abstract: OBJECTIVE
  Neural tube defects (NTDs) occur in 1:1000 births. The etiology is complex, with the influence of environmental and genetic factors. Environmental factors, such as folate deficiency, diabetes, or hypoxia strongly contribute to the occurrence of NTD. Also, there is a strong genetic contribution to NTD, as highlighted by the number of genes so far identified in several different developmental pathways usually altered in NTD. Each gene identified so far accounts for a small percentage of all NTD cases, indicating a very high heterogeneity.
  
  
  METHODS
  Exome sequencing was performed in seven sporadic patients with severe mielomeningocele. Novel coding variants shared by two or more patients were selected for further analysis.
  
  
  RESULTS
  We identified in two unrelated patients two different variants in TNIP1, a gene not previously involved in NTD whose main role is downregulation of the NF-kB pathway. One variant, c.1089T>G (p.Phe363Leu), is de novo, whereas the c.1781C>T (p.Pro594Leu) is absent in the mother, but could not be tested in the father, as he was unavailable. The latter variant is a very rare variant in the ExAC database.
  
  
  CONCLUSIONS
  These findings suggest that TNIP1 is a new potential predisposing gene to spina bifida (SB) and its pathway needs to be investigated in human NTD in order to confirm its role and to plan appropriate counseling to families.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, Columbia, NY, USA.
authors.forename: La Carpia
authors.initials: LC
authors.lastname: Francesca
authors.affiliation: Istituto di Pediatria, Università Cattolica del Sacro Cuore "A. Gemelli", Rome, Italy.
authors.forename: Rendeli
authors.initials: R
authors.lastname: Claudia
authors.affiliation: Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore "A. Gemelli", L.go Francesco Vito 1, 00168, Rome, Italy.
authors.forename: Clelia
authors.initials: C
authors.lastname: Molinario
authors.affiliation: Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore "A. Gemelli", L.go Francesco Vito 1, 00168, Rome, Italy.
authors.forename: Milillo
authors.initials: M
authors.lastname: Annamaria
authors.affiliation: Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore "A. Gemelli", L.go Francesco Vito 1, 00168, Rome, Italy.
authors.forename: Farroni
authors.initials: F
authors.lastname: Chiara
authors.affiliation: Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore "A. Gemelli", L.go Francesco Vito 1, 00168, Rome, Italy.
authors.forename: Cannelli
authors.initials: C
authors.lastname: Natalia
authors.affiliation: Istituto di Pediatria, Università Cattolica del Sacro Cuore "A. Gemelli", Rome, Italy.
authors.forename: Ausili
authors.initials: A
authors.lastname: Emanuele
authors.affiliation: Istituto di Pediatria, Università Cattolica del Sacro Cuore "A. Gemelli", Rome, Italy.
authors.forename: Paolucci
authors.initials: P
authors.lastname: Valentina
authors.affiliation: Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore "A. Gemelli", L.go Francesco Vito 1, 00168, Rome, Italy.
authors.forename: Neri
authors.initials: N
authors.lastname: Giovanni
authors.affiliation: Istituto di Pediatria, Università Cattolica del Sacro Cuore "A. Gemelli", Rome, Italy.
authors.forename: Romagnoli
authors.initials: R
authors.lastname: Costantino
authors.affiliation: Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore "A. Gemelli", L.go Francesco Vito 1, 00168, Rome, Italy.
authors.forename: Sangiorgi
authors.initials: S
authors.lastname: Eugenio
authors.affiliation: Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore "A. Gemelli", L.go Francesco Vito 1, 00168, Rome, Italy. fiorella.gurrieri@unicatt.it.
authors.forename: Gurrieri
authors.initials: G
authors.lastname: Fiorella
mesh_terms: D002460:Cell Line; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009436:Neural Tube Defects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C498143:RELA protein, human; C117046:TNIP1 protein, human; D051996:Transcription Factor RelA
keywords: Exome sequencing; Spina bifida; TNIP1