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. 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. 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. 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.

Variants in TNIP1, a regulator of the NF-kB pathway, found in two patients with neural tube defects

Gurrieri F
2016-01-01

Abstract

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. 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. 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. 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/5370
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