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

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An Erratum to this article was published on 18 May 2016

Abstract

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.

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Acknowledgments

We thank the families for contributing to our studies and the Association “La Strada per l’Arcobaleno” for funding it.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pathology and Cell Biology, Columbia University Medical Center, Columbia, NY, USA

    La Carpia Francesca

  2. Istituto di Pediatria, Università Cattolica del Sacro Cuore “A. Gemelli”, Rome, Italy

    Rendeli Claudia, Ausili Emanuele, Paolucci Valentina & Romagnoli Costantino

  3. Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore “A. Gemelli”, L.go Francesco Vito 1, 00168, Rome, Italy

    Clelia Molinario, Milillo Annamaria, Farroni Chiara, Cannelli Natalia, Neri Giovanni, Sangiorgi Eugenio & Gurrieri Fiorella

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  1. La Carpia Francesca
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Francesca, L.C., Claudia, R., Molinario, C. et al. Variants in TNIP1, a regulator of the NF-kB pathway, found in two patients with neural tube defects. Childs Nerv Syst 32, 1061–1067 (2016). https://doi.org/10.1007/s00381-016-3087-1

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  • DOI: https://doi.org/10.1007/s00381-016-3087-1

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