Article

The worldwide incidence of neural tube defects (NTDs) ranges from 1.0 to 10.0 per 1,000 births with almost equal frequencies between two major categories:
anencephaly and spina bifida (SB). Epidemiological studies have provided valuable
insight for (a) researchers to identify nongenetic and genetic factors
contributing to etiology, (b) public health officials to design and implement
policies to prevent NTD pregnancies, and (c) individuals to take precautions to
reduce the chance of having an NTD-affected pregnancy. Despite extensive
research, our knowledge of the genetic etiology of human NTDs is limited.
Although more than 200 small animal models with NTDs exist, most of these models
do not replicate the human disease phenotype. Over a hundred candidate genes have
been examined for risk association to human SB. The candidate genes studied
include those important in folic acid metabolism, glucose metabolism, retinoid
metabolism, and apoptosis. Many genes that regulate transcription in early
embryogenesis and maintain planar cell polarity have also been tested as
candidates. Additionally, genes identified through mouse models of NTDs have been
explored as candidates. We do not know how many genes in the human genome may
confer risk for NTDs in human.
Less than 20% of the studied candidate genes have
been determined to confer even a minor effect on risk association. Many studies
have provided conflicting conclusions due to limitations in study design that
potentially affect the power of statistical analysis. Future directions such as
genomewide association studies (GWAS) and whole exome or even whole genome
sequencing are discussed as possible avenues to identify genes that affect risk for human NTDs.

Langue : ANGLAIS