Human Neural Tube Research Articles

Identifying environmental risk factors for human neural tube defects before and after folic acid supplementation.

BackgroundBirth defects are a major cause of infant mortality and disability in many parts of the world. Neural tube defects (NTDs) are one of the most common types of birth defects. In 2001, the Chinese population and family planning commission initiated a national intervention program for the prevention of birth defects. A key step in the program was the introduction of folic acid supplementation. Of interest in the present study was to determine whether folic acid supplementation has the same protective effect on NTDs under various geographical and socioeconomic conditions within the Chinese population and the nature in which the influence of environmental factors varied after folic acid supplementation.MethodsIn this study, Heshun was selected as the region of interest as a surrogate for helping to answer some of the questions raised in this study on the impact of the intervention program. Spatial filtering in combination with GIS software was used to detect annual potential clusters from 1998 to 2005 in Heshun, and Kruskal-wallis test and multivariate regression were applied to identify the environmental risk factors for NTDs among various regions.ResultsIn 1998, a significant (p < 0.100) NTDs cluster was detected in the west of Heshun. After folic acid supplementation, the significant clusters gradually moved from west to east. However, during the study period, most of the clusters appeared in the middle region of Heshun where more than 95 percent of the coal mines of Heshun are located. For the analysis, buffer regions of the coal mine zone were built in a GIS environment. It was found that the correlations between environmental risk factors and NTDs vary among the buffer regions.ConclusionThis suggests that the government needs to adapt the intervention measures according to local conditions. More attention needs to be paid to the poor and to people living in areas near coal mines.

Genetics of human neural tube defects

Neural tube defects (NTDs) are common, severe congenital malformations whose causation involves multiple genes and environmental factors. Although more than 200 genes are known to cause NTDs in mice, there has been rather limited progress in delineating the molecular basis underlying most human NTDs. Numerous genetic studies have been carried out to investigate candidate genes in cohorts of patients, with particular reference to those that participate in folate one-carbon metabolism. Although the homocysteine remethylation gene MTHFR has emerged as a risk factor in some human populations, few other consistent findings have resulted from this approach. Similarly, attention focused on the human homologues of mouse NTD genes has contributed only limited positive findings to date, although an emerging association between genes of the non-canonical Wnt (planar cell polarity) pathway and NTDs provides candidates for future studies. Priorities for the next phase of this research include: (i) larger studies that are sufficiently powered to detect significant associations with relatively minor risk factors; (ii) analysis of multiple candidate genes in groups of well-genotyped individuals to detect possible gene–gene interactions; (iii) use of high throughput genomic technology to evaluate the role of copy number variants and to detect ‘private’ and regulatory mutations, neither of which have been studied to date; (iv) detailed analysis of patient samples stratified by phenotype to enable, for example, hypothesis-driven testing of candidates genes in groups of NTDs with specific defects of folate metabolism, or in groups of fetuses with well-defined phenotypes such as craniorachischisis.

Folate rescues lithium-, homocysteine- and Wnt3A-induced vertebrate cardiac anomalies.

Elevated plasma homocysteine (HCy), which results from folate (folic acid, FA) deficiency, and the mood-stabilizing drug lithium (Li) are both linked to the induction of human congenital heart and neural tube defects. We demonstrated previously that acute administration of Li to pregnant mice on embryonic day (E)6.75 induced cardiac valve defects by potentiating Wnt-beta-catenin signaling. We hypothesized that HCy may similarly induce cardiac defects during gastrulation by targeting the Wnt-beta-catenin pathway. Because dietary FA supplementation protects from neural tube defects, we sought to determine whether FA also protects the embryonic heart from Li- or HCy-induced birth defects and whether the protection occurs by impacting Wnt signaling. Maternal elevation of HCy or Li on E6.75 induced defective heart and placental function on E15.5, as identified non-invasively using echocardiography. This functional analysis of HCy-exposed mouse hearts revealed defects in tricuspid and semilunar valves, together with altered myocardial thickness. A smaller embryo and placental size was observed in the treated groups. FA supplementation ameliorates the observed developmental errors in the Li- or HCy-exposed mouse embryos and normalized heart function. Molecular analysis of gene expression within the avian cardiogenic crescent determined that Li, HCy or Wnt3A suppress Wnt-modulated Hex (also known as Hhex) and Islet-1 (also known as Isl1) expression, and that FA protects from the gene misexpression that is induced by all three factors. Furthermore, myoinositol with FA synergistically enhances the protective effect. Although the specific molecular epigenetic control mechanisms remain to be defined, it appears that Li or HCy induction and FA protection of cardiac defects involve intimate control of the canonical Wnt pathway at a crucial time preceding, and during, early heart organogenesis.

Recent perspectives on the development of the central nervous system and the genetic background of neural tube defects

Neural tube defects are rare and mostly lethal malformations. The pattern of inheritance of these malformations is multifactorial, rendering the identification of the underlying causes. Numerous studies have been conducted to elucidate the genetic basis of the development of the central nervous system. Essential signaling pathways of the development of the central nervous system include the planar cell polarity pathway, which is important for the initiation of neural tube closure as well as sonic hedgehog pathway, which regulates the neural plate bending. Genes and their mutations influencing the different stages of neurulation have been investigated for their eventual role in the development of these malformations. Among the environmental factors, folic acid seems to be the most important modifier of the risk of human neural tube defects. Genes of the folate metabolism pathways have also been investigated to identify mutations resulting in increased risk of NTDs. In this review the author has attempted to summarize the knowledge on neural tube defects, with special regard to genetic factors of the etiology.

Recent perspectives on the genetic background of neural tube defects with special regard to iniencephaly

Iniencephaly is a rare and mostly lethal type of neural tube defect. The pattern of inheritance of this group of malformations is multifactorial, rendering the identification of the underlying causes. Numerous studies have been conducted to elucidate the genetic basis of human neurulation. Essential signaling pathways of the development of the CNS include the planar cell polarity pathway, which is important for the initiation of neural tube closure, as well as the sonic hedgehog pathway, which regulates the neural plate bending. Genes influencing the different stages of neurulation have been investigated for their eventual role in the development of these malformations. Among the environmental factors, folic acid seems to be the most important modifier of the risk of human neural tube defects. Genes of the folate metabolism pathways have also been investigated to identify mutations resulting in increased risk of neural tube defects. In this review we have attempted to summarize the knowledge on iniencephaly and neural tube defects, with special regard to genetic factors of the etiology.

The search for genetic polymorphisms in the homocysteine/folate pathway that contribute to the etiology of human neural tube defects

In this paper, we trace the history of current research into the genetic and biochemical mechanisms that underlie folate-preventable neural tube defects (NTDs). The inspired suggestion by Smithells that common vitamins might prevent NTDs ignited a decade of biochemical investigations-first exploring the nutritional and metabolic factors related to NTDs, then onto the hunt for NTD genes. Although NTDs were known to have a strong genetic component, the concept of common genetic variance being linked to disease risk was relatively novel in 1995, when the first folate-related polymorphism associated with NTDs was discovered. The realization that more genes must be involved started a rush to find polymorphic needles in genetic haystacks. Early efforts entailed the intellectually challenging and time-consuming task of identifying and analyzing candidate single nucleotide polymorphisms (SNPs) in folate pathway genes. Luckily, human genome research has developed rapidly, and the search for the genetic factors that contribute to the etiology of human NTDs has evolved to mirror the increased level of knowledge and data available on the human genome. Large-scale candidate gene analysis and genome-wide association studies are now readily available. With the technical hurdles removed, the remaining challenge is to gather a sample large enough to uncover the polymorphisms that contribute to NTD risk. In some respects the real work is beginning. Although moving forward is exciting, it is humbling that the most important result-prevention of NTDs by maternal folic acid supplementation-was achieved years ago, the direct result of Smithells' groundbreaking studies.

Risk assessment of human neural tube defects using a Bayesian belief network

Neural tube defects (NTDs) constitute the most common type of birth defects. How much risk of NTDs could an area take? The answer to this question will help people understand the geographical distribution of NTDs and explore its environmental causes. Most existing methods usually take the spatial correlation of cases into account and rarely consider the effect of environmental factors. However, especially in rural areas, the NTDs cases have a little effect on each other across space, whereas the role of environmental factors is significant. To demonstrate these points, Heshun, a county with the highest rate of NTDs in China, was selected as the region of interest in the study. Bayesian belief network was used to quantify the probability of NTDs occurred at villages with no births. The study indicated that the proposed method was easy to apply and high accuracy was achieved at a 95% confidence level.

Insights into prevention of human neural tube defects by folic acid arising from consideration of mouse mutants

Almost 30 years after the initial study by Richard W. Smithells and coworkers, it is still unknown how maternal periconceptional folic acid supplementation prevents human neural tube defects (NTDs). In this article, questions about human NTD prevention are considered in relation to three groups of mouse models: NTD mutants that respond to folate, NTD mutants and strains that do not respond to folate, and mutants involving folate-pathway genes. Of the 200 mouse NTD mutants, only a few have been tested with folate; half respond and half do not. Among responsive mutants, folic acid supplementation reduces exencephaly and/or spina bifida aperta frequency in the Sp(2H), Sp, Cd, Cited2, Cart1, and Gcn5 mutants. Prevention ranges from 35 to 85%. The responsive Sp(2H) (Pax3) mutant has abnormal folate metabolism, but the responsive Cited2 mutant does not. Neither folic nor folinic acid reduces NTD frequency in Axd, Grhl3, Fkbp8, Map3k4, or Nog mutants or in the curly tail or SELH/Bc strains. Spina bifida frequency is reduced in Axd by methionine and in curly tail by inositol. Exencephaly frequency is reduced in SELH/Bc by an alternative commercial ration. Mutations in folate-pathway genes do not cause NTDs, except for 30% exencephaly in folate-treated Folr1. Among folate-pathway mutants, neural tube closure is normal in Cbs, Folr2, Mthfd1, Mthfd2, Mthfr, and Shmt1 mutants. Embryos die by midgestation in Folr1, Mtr, Mtrr, and RFC1 mutants. The mouse models point to genetic heterogeneity in the ability to respond to folic acid and also to heterogeneity in genetic cause of NTDs that can be prevented by folic acid.

Further evidence for a maternal genetic effect and a sex‐influenced effect contributing to risk for human neural tube defects

Neural tube defects (NTDs), including spina bifida and anencephaly, are the second most common birth defect with an incidence of 1/1000. Genetic factors are believed to contribute to NTD risk and family-based studies can be useful for identifying such risk factors. We ascertained 1066 NTD families (1467 affected patients), including 307 multiplex NTD families. We performed pedigree analysis to describe the inheritance patterns, pregnancy outcomes, and recurrence risks to relatives of various types. Myelomeningocele or spina bifida (66.9%) and cranial defects (17.7%) were the most common NTD subtypes observed. The overall male:female ratio for affected individuals was 0.82, and there were even fewer males among individuals with an upper level NTD (0.62). Among twins, 2 of the 5 monozygotic twins and only 3 of 35 dizygotic twins were concordant, while 27% of the same sex twins were concordant, but none of the different sex twins. The estimated 6.3% recurrence risk to siblings (CI 0.04-0.08) is consistent with previous reports. Families with two or more affected individuals show a higher proportion of female transmitters (p = 0.0002). Additionally, the number of affected relatives in maternal compared to paternal lineages was more than double (p = 0.006). There were significantly more miscarriages, infant deaths, and stillborn pregnancies of the maternal aunts and uncles (p < 0.0001) and of first cousins (p = 0.04). Our data provide several lines of evidence consistent with a maternal effect, as well as a sex-influenced effect, in the etiology of NTDs.

Involvement of the axially condensed tail bud mesenchyme in normal and abnormal human posterior neural tube development

Development of the posterior neural tube (PNT) in human embryos is a complicated process which involves both primary and secondary neurulation. Normal development of the human PNT should be understood to elucidate the pathogenesis of spinal neural tube defects, but there have been some discrepancies among previous reports. We examined histologically 20 human embryos around the stage of the posterior neuropore closure and found that the developing PNT can be divided into three parts: (1) the most rostral region which corresponds to the posterior part of the primary neural tube; (2) the junctional region of the primary and secondary neural tubes; and (3) the caudal region which emerges from the neural cord. In the junctional region, the axially condensed mesenchyme (AM) intervened between the neural plate/tube and the notochord. The AM appeared to be incorporated into the most ventral part of the primary neural tube, and no cavity was observed in the AM. Interestingly, we found three cases of human embryos with lumbosacral myeloschisis in which the open primary neural tube and the closed secondary neural tube overlapped dorso-ventrally. The open and closed neural tubes appeared to be part of the primary and the AM-derived secondary neural tubes, respectively. Thus, these findings suggest that in embryos with lumbosacral myeloschisis, the AM may not be incorporated into the ventral part of the primary neural tube but aberrantly differentiate into the secondary neural tube containing cavities, leading to dorso-ventral overlapping of the primary and secondary neural tubes. These findings suggest that the AM in human embryos plays some role in normal and abnormal development of the human posterior neural tube.

Nodal signaling is required for closure of the anterior neural tube in zebrafish

BackgroundNodals are secreted signaling proteins with many roles in vertebrate development. Here, we identify a new role for Nodal signaling in regulating closure of the rostral neural tube of zebrafish.ResultsWe find that the neural tube in the presumptive forebrain fails to close in zebrafish Nodal signaling mutants. For instance, the cells that will give rise to the pineal organ fail to move from the lateral edges of the neural plate to the midline of the diencephalon. The open neural tube in Nodal signaling mutants may be due in part to reduced function of N-cadherin, a cell adhesion molecule expressed in the neural tube and required for neural tube closure. N-cadherin expression and localization to the membrane are reduced in fish that lack Nodal signaling. Further, N-cadherin mutants and morphants have a pineal phenotype similar to that of mutants with deficiencies in the Nodal pathway. Overexpression of an activated form of the TGFβ Type I receptor Taram-A (Taram-A*) cell autonomously rescues mesendoderm formation in fish with a severe decrease in Nodal signaling. We find that overexpression of Taram-A* also corrects their open neural tube defect. This suggests that, as in mammals, the mesoderm and endoderm have an important role in regulating closure of the anterior neural tube of zebrafish.ConclusionThis work helps establish a role for Nodal signals in neurulation, and suggests that defects in Nodal signaling could underlie human neural tube defects such as exencephaly, a fatal condition characterized by an open neural tube in the anterior brain.

Genetic models of mammalian neural tube defects.

Several mouse mutations disturb the embryonic process of neurulation, yielding neural tube defects. Analysis of the mutations offers the most feasible approach to understanding the aetiology and pathogenesis of human neural tube defects. Interactions between the non-allelic mutant genes and between several of the mutant genes and modifying genes in the genetic background modulate the frequency and severity of the defects that develop. Environmental factors interact with the genetic predisposition either to increase or to decrease the incidence of defects. The gene loci corresponding to two of the mutations, splotch (Sp) and extra toes (Xt), have been identified as those encoding the transcription factors Pax-3 and Gli3, respectively; their human homologues are associated with Waardenburg type I syndrome and Greig's cephalopolysyndactyly. Embryological analysis reveals that several of the mutations disturb the process of neural tube closure at the posterior neuropore (in the lumbosacral region), yielding spina bifida and/or tail defects. The different mutations appear to achieve this developmental end-point by different underlying mechanisms. In curly tail (ct), non-neural tissues proliferate abnormally slowly causing ventral curvature of the neuropore region and inhibiting neural tube closure. Neural tube defects can be prevented in cultured ct/ct embryos by experimentally correcting either the proliferative imbalance or the ventral curvature. In Sp the primary defect appears to reside in the neuroepithelium. A combination of genetic analysis, gene cloning and experimental embryology is revealing that neural tube defects in mice and, by implication, in humans are a developmentally heterogeneous group of malformations.

A Relevant Animal Model of Human Neural Tube Defects, Implications for Fetal Surgery

A Relevant Animal Model of Human Neural Tube Defects, Implications for Fetal Surgery

The Hectd1 ubiquitin ligase is required for development of the head mesenchyme and neural tube closure

Closure of the cranial neural tube depends on normal development of the head mesenchyme. Homozygous-mutant embryos for the ENU-induced open mind ( opm) mutation exhibit exencephaly associated with defects in head mesenchyme development and dorsal-lateral hinge point formation. The head mesenchyme in opm mutant embryos is denser than in wildtype embryos and displays an abnormal cellular organization. Since cells that originate from both the cephalic paraxial mesoderm and the neural crest populate the head mesenchyme, we explored the origin of the abnormal head mesenchyme. opm mutant embryos show apparently normal development of neural crest-derived structures. Furthermore, the abnormal head mesenchyme in opm mutant embryos is not derived from the neural crest, but instead expresses molecular markers of cephalic mesoderm. We also report the identification of the opm mutation in the ubiquitously expressed Hectd1 E3 ubiquitin ligase. Two different Hectd1 alleles cause incompletely penetrant neural tube defects in heterozygous animals, indicating that Hectd1 function is required at a critical threshold for neural tube closure. This low penetrance of neural tube defects in embryos heterozygous for Hectd1 mutations suggests that Hectd1 should be considered as candidate susceptibility gene in human neural tube defects.

Aberrant differentiation of the axially condensed tail bud mesenchyme in human embryos with lumbosacral myeloschisis

Development of the posterior neural tube (PNT) in human embryos is a complicated process that involves both primary and secondary neurulation. Recently, we histologically examined 20 human embryos around the stage of posterior neuropore closure and found that the axially condensed mesenchyme (AM) intervened between the neural plate/tube and the notochord in the junctional region of the primary and secondary neural tubes. The AM appeared to be incorporated into the most ventral part of the primary neural tube, and no cavity was observed in the AM. In this study, we report three cases of human embryos with myeloschisis in which the open primary neural tube and the closed secondary neural tube overlap dorsoventrally. In all three cases, part of the closed neural tube was located ventrally to the open neural tube in the lumbosacral region. The open and closed neural tubes appeared to be part of the primary and the AM-derived secondary neural tubes, respectively. Thus, these findings suggest that, in those embryos with myeloschisis, the AM may not be incorporated into the ventral part of the primary neural tube but aberrantly differentiate into the secondary neural tube containing cavities, leading to dorsoventral overlapping of the primary and secondary neural tubes. The aberrant differentiation of the AM in embryos with lumbosacral myeloschisis suggests that the AM plays some roles in normal as well as abnormal development of the human posterior neural tube.

Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects

The number of mouse mutants and strains with neural tube closure defects (NTDs) now exceeds 190, including 155 involving known genes, 33 with unidentified genes, and eight "multifactorial" strains. The emerging patterns of mouse NTDs are considered in relation to the unknown genetics of the common human NTDs, anencephaly, and spina bifida aperta. Of the 150 mouse mutants that survive past midgestation, 20% have risk of either exencephaly and spina bifida aperta or both, parallel to the majority of human NTDs, whereas 70% have only exencephaly, 5% have only spina bifida, and 5% have craniorachischisis. The primary defect in most mouse NTDs is failure of neural fold elevation. Most null mutations (>90%) produce syndromes of multiple affected structures with high penetrance in homozygotes, whereas the "multifactorial" strains and several null-mutant heterozygotes and mutants with partial gene function (hypomorphs) have low-penetrance nonsyndromic NTDs, like the majority of human NTDs. The normal functions of the mutated genes are diverse, with clusters in pathways of actin function, apoptosis, and chromatin methylation and structure. The female excess observed in human anencephaly is found in all mouse exencephaly mutants for which gender has been studied. Maternal agents, including folate, methionine, inositol, or alternative commercial diets, have specific preventative effects in eight mutants and strains. If the human homologs of the mouse NTD mutants contribute to risk of common human NTDs, it seems likely to be in multifactorial combinations of hypomorphs and low-penetrance heterozygotes, as exemplified by mouse digenic mutants and the oligogenic SELH/Bc strain.

The folate metabolic enzyme ALDH1L1 is restricted to the midline of the early CNS, suggesting a role in human neural tube defects

Folate supplementation prevents up to 70% of human neural tube defects (NTDs), although the precise cellular and metabolic sites of action remain undefined. One possibility is that folate modulates the function of metabolic enzymes expressed in cellular populations involved in neural tube closure. Here we show that the folate metabolic enzyme ALDH1L1 is cell-specifically expressed in PAX3-negative radial glia at the midline of the neural tube during early murine embryogenesis. Midline restriction is not a general property of this branch of folate metabolism, as MTHFD1 displays broad and apparently ubiquitous expression throughout the neural tube. Consistent with previous work showing antiproliferative effects in vitro, ALDH1L1 upregulation during central nervous system (CNS) development correlates with reduced proliferation and most midline ALDH1L1(+) cells are quiescent. These data provide the first evidence for localized differences in folate metabolism within the early neural tube and suggest that folate might modulate proliferation via effects on midline Aldh1l1(+) cells. To begin addressing its role in neurulation, we analyzed a microdeletion mouse strain lacking Aldh1l1 and observed neither increased failure of neural tube closure nor detectable proliferation defects. Although these results indicate that loss-of-function Aldh1l1 mutations do not impair these processes in mice, the specific midline expression of ALDH1L1 and its ability to dominantly suppress proliferation in a folate responsive manner may suggest that mutations contributing to disease are gain-of-function, rather than loss-of-function. Moreover, a role for loss-of-function mutations in human NTDs remains possible, as Mthfr null mice do not develop NTDs even though MTHFR mutations increase human NTD risk.

Bladder and External Urethral Sphincter Function After Prenatal Closure of Myelomeningocele

We compared urodynamic findings in patients who underwent prenatal closure of myelomeningocele with those of patients who underwent postnatal closure, and equivalent lower urinary tract evaluations. Urodynamic studies of 5 patients (2 boys, 3 girls) who underwent prenatal closure of myelomeningocele were compared to those of 88 patients with similar level lesions who underwent repair postnatally between 1979 and 2002. All 5 patients in the prenatally treated cohort had lower lumbosacral lesions on neurological examination. These patients displayed no evidence of electromyographic activity, indicating complete denervation of the external sphincter. In comparison 34 of the 88 patients in the postnatal cohort (39%) lacked sphincter activity at newborn examination, with similar findings noted at 1-year evaluation. In terms of bladder function all 5 patients in the prenatal cohort exhibited detrusor overactivity, compared to 33 of the 88 patients (38%) in the postnatal cohort at the newborn examination, with similar findings at 1-year evaluation. Fetal closure of myelomeningocele is associated with a higher incidence of complete denervation of the external urethral sphincter and detrusor overactivity compared to postnatal closure. Patients who undergo this novel procedure should undergo urodynamic studies in the immediate newborn period and should be under close postnatal surveillance to document possible tethering of the spinal cord, urinary incontinence and increased detrusor pressures.

Current perspectives on the genetic causes of neural tube defects

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.

Advances of Liquid Chromatographic Determination of Fumonisins; Potential Mycotoxins for Humans

Fumonisins, first identified in 1988, are naturally-occurring mycotoxins mainly produced by Fusarium verticillioides and F. proliferatum, food-borne fungi widely distributed in crops, and occur as one of the most common contaminants of corn and corn-based foods and feeds. The most abundant fumonisin, fumonisin B1 (FB1), is associated with a range of toxicological effects in animals including equine leukoencephalomalacia, porcine pulmonary edema, and rodent carcinogenicity. In humans, FB1 has been associated with high rates of esophageal cancer and the International Agency for Research on Cancer evaluated the FB1 derived from F. verticililoides as Group 2B, i.e. a possible human carcinogen. Furthermore, FB1 has been found to be a potential cause of human neural tube defects. Fumonisins bear a remarkable structural similarity to sphingosine and their mode of toxic action is in part elucidated in that they may inhibit ceramide synthase, causing accumulation of bioactive intermediates of sphingolipid metabolism. In spite of the need for efficient analysis, the quantification of fumonisins is a difficult task, since they do not bear suitable chromophores nor fluorophores for detection. Practical fluorometric-based high-performance liquid chromatography analysis methods for derivatized fumonisins have been developed since 1990 and a method using o-phthalaldehyde as a fluorescent reagent has been validated. Recently, mass spectrometry analysis has been used to identify fumonisins as liquid chromatography-mass spectrometry interfaces became more widely available. This appears to be the superior method to perform quantitative and qualitative analysis without the need of derivatization procedures. Very recently, the application of tandem mass spectrometry for confirmation and quantification of mycotoxins including fumonisins has been reported. This paper reviews those liquid chromatographic methods developed for this group of mycotoxins. Keywords: Fumonisin, Analysis, Liquid chromatography, Fluorescence, Derivatization, Mass spectrometry