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Current perspectives on the genetic causes of neural tube defects

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Abstract

Neural tube defects (NTDs) are a group of severe congenital abnormalities resulting from the failure of neurulation. The pattern of inheritance of these complex defects is multifactorial, making it difficult to identify the underlying causes. Scientific research has rapidly progressed in experimental embryology and molecular genetics to elucidate the basis of neurulation. Crucial mechanisms of neurulation include the planar cell polarity pathway, which is essential for the initiation of neural tube closure, and the sonic hedgehog signaling pathway, which regulates neural plate bending. Genes influencing neurulation have been investigated for their contribution to human neural tube defects, but only genes with well-established role in convergent extension provide an exciting new set of candidate genes. Biochemical factors such as folic acid appear to be the greatest modifiers of NTDs risk in the human population. Consequently, much research has focused on genes of folate-related metabolic pathways. Variants of several such genes have been found to be significantly associated with the risk of neural tube defects in more studies. In this manuscript, we reviewed the current perspectives on the causes of neural tube defects and highlighted that we are still a long way from understanding the etiology of these complex defects.

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Abbreviations

NTDs:

Neural tube defects

AED:

Antiepileptic drug

CRs:

Cysteine-rich domains

BMP:

Bone morphogenetic protein

FGF:

Fibroblast growth factor

FGFR:

Fibroblast growth factor receptor

IGF:

Insulin-like growth factor

DV:

Dorsoventral

AP:

Anteroposterior

RA:

Retinoic acid

Shh:

Sonic hedgehog

b-HLH:

Basic helix-loop-helix

RARs:

Retinoic acid receptors

PCP:

Planar cell polarity

MHP:

Median hinge point

DLHPs:

Dorsolateral hinge points

GCPS:

Greig cephalopolysyndactyly syndrome

HPE:

Holoprosencephaly

BM:

Body mass

Hcy:

Homocysteine

THF:

Tetrahydrofolate

LDL:

Low-density lipoprotein

PKC:

Protein kinase C

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Acknowledgements

The authors would like to thank A.J. Copp for his helpful discussion. P.D.M., E.M., and S.M. are supported by grants of Italian Ministry of Health. V.C. is supported by Gaslini Foundation.

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  1. U.O. Neurochirurgia, Istituto G. Gaslini, Largo G. Gaslini 5, 16148, Genova, Italy

    Patrizia De Marco, Elisa Merello, Samantha Mascelli & Valeria Capra

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  1. Patrizia De Marco
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  2. Elisa Merello
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  3. Samantha Mascelli
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  4. Valeria Capra
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Correspondence to Valeria Capra.

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De Marco, P., Merello, E., Mascelli, S. et al. Current perspectives on the genetic causes of neural tube defects. Neurogenetics 7, 201–221 (2006). https://doi.org/10.1007/s10048-006-0052-2

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