PURPOSE: 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.
PURPOSE: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 humanNTD in order to confirm its role and to plan appropriate counseling to families.
Authors: Zoha Kibar; Elena Torban; Jonathan R McDearmid; Annie Reynolds; Joanne Berghout; Melissa Mathieu; Irena Kirillova; Patrizia De Marco; Elisa Merello; Julie M Hayes; John B Wallingford; Pierre Drapeau; Valeria Capra; Philippe Gros Journal: N Engl J Med Date: 2007-04-05 Impact factor: 91.245
Authors: Ciprian M Bosoi; Valeria Capra; Redouane Allache; Vincent Quoc-Huy Trinh; Patrizia De Marco; Elisa Merello; Pierre Drapeau; Alexander G Bassuk; Zoha Kibar Journal: Hum Mutat Date: 2011-09-23 Impact factor: 4.878
Authors: E C Melvin; T M George; G Worley; A Franklin; J Mackey; K Viles; N Shah; C R Drake; D S Enterline; D McLone; J Nye; W J Oakes; C McLaughlin; M L Walker; P Peterson; T Brei; C Buran; J Aben; B Ohm; I Bermans; M Qumsiyeh; J Vance; M A Pericak-Vance; M C Speer Journal: Pediatr Neurosurg Date: 2000-01 Impact factor: 1.162
Authors: Kristen L Deak; Deborah G Siegel; Timothy M George; Simon Gregory; Allison Ashley-Koch; Marcy C Speer Journal: Birth Defects Res A Clin Mol Teratol Date: 2008-10