MyMedR

Uncovering neural tube defects in humans through candidate gene expression patterns in mouse embryos

Nor Linda Abdullah, Mustakiza Muslimin, Hoo, Wan Mun, Fahimah Noor Ngah, Sheikh Mohd Norhafiz Abdul Aziz, Nor Syazwani Yip, et al.

Orient Neuron Nexus, 2010;1(1):2-6.

MyJurnal

Neural tube defects (NTDs) are the leading cause of disability in humans arising from the malformation of the central nervous system. The genes responsible and their involvement in causing neural tube defects in humans are poorly understood. Gene expression analysis in a whole organism enables the identification of the possible role of the gene being studied. If the gene is expressed in a particular tissue at a certain period of development, this spatiotemporal pattern of the gene of interest signals the possibility that the gene serves a function of being switched on in those tissues at that particular time. In this report, we have identified possible gene candidates in the mouse which may be required for the development of the neural tube, the precursor to the brain and the spinal cord. Development of the brain occurs by closure of the anterior neuropore (forms the cranial neural tube) while the spinal cord forms due to resolution of the posterior neuropore (forms the caudal neural tube). The genes Tiaml and T-cadherin were found to be likely candidate genes for the development of the spinal cord and may serve as potential human NTDs genes.

Matched MeSH terms: Neural Tube Defects; Neural Tube

Fulltext A Novel Occulta-Type Spina Bifida Mediated by Murine Double Heterozygotes EphA2 and EphA4 Receptor Tyrosine Kinases

Abdullah NL, Mohd-Zin SW, Ahmad-Annuar A, Abdul-Aziz NM

Front Cell Dev Biol, 2017;5:105.

PMID: 29312933 DOI: 10.3389/fcell.2017.00105

Members of the Eph receptor tyrosine kinase have previously been implicated in cranial neural tube development. Failure of neural tube closure leads to the devastating conditions known as anencephaly and spina bifida. EphA2 and EphA4 are expressed at the tips of the closing spinal neural folds prior and during neural tube closure. We investigated the possible role of murine EphA2 and EphA4 during the last step of primary neural tube closure, which is adhesion and fusion. The individual mouse knockouts of EphA2 and EphA4 per se do not exhibit neural tube defects (NTDs). The embryos generated by the crossing of double heterozygotes Epha2tm1Jrui/+Epha4rb-2J/+ displayed NTDs with a wide degree of severity including close exencephaly and close spina bifida (spina bifida occulta). Interestingly, mutants displaying NTDs had skin covering the underlying lesion. The tissue sections revealed the elevated neural folds had not adhered and fused. The phenotypes seen in Epha2tm1Jrui/+Epha4rb-2J/+ double heterozygous embryos suggest both genes play a compensatory role with each other in the adhesion and fusion of the neural tube. In this study, there exists a >50% penetrance of NTDs in the mouse mutants, which genetically have a single allele each of EphA2 and EphA4 absent.

Matched MeSH terms: Neural Tube Defects; Neural Tube

Fulltext Epithelial fusion during neural tube morphogenesis

Pai YJ, Abdullah NL, Mohd-Zin SW, Mohammed RS, Rolo A, Greene ND, et al.

Birth Defects Res. Part A Clin. Mol. Teratol., 2012 Oct;94(10):817-23.

PMID: 22945349 DOI: 10.1002/bdra.23072

Adhesion and fusion of epithelial sheets marks the completion of many morphogenetic events during embryogenesis. Neural tube closure involves an epithelial fusion sequence in which the apposing neural folds adhere initially via cellular protrusions, proceed to a more stable union, and subsequently undergo remodeling of the epithelial structures to yield a separate neural tube roof plate and overlying nonneural ectoderm. Cellular protrusions comprise lamellipodia and filopodia, and studies in several different systems emphasize the critical role of RhoGTPases in their regulation. How epithelia establish initial adhesion is poorly understood but, in neurulation, may involve interactions between EphA receptors and their ephrinA ligands. Epithelial remodeling is spatially and temporally correlated with apoptosis in the dorsal neural tube midline, but experimental inhibition of this cell death does not prevent fusion and remodeling. A variety of molecular signaling systems have been implicated in the late events of morphogenesis, but genetic redundancy, for example among the integrins and laminins, makes identification of the critical players challenging. An improved understanding of epithelial fusion can provide insights into normal developmental processes and may also indicate the mode of origin of clinically important birth defects.

Matched MeSH terms: Neural Tube/embryology*; Neural Tube/metabolism; Neural Tube/physiology

Neurenteric cyst of the cervicothoracic junction: A rare cause of paraparesis in a paediatric patient

Sheaufung S, Taufiq A, Nawawi O, Naicker MS, Waran V

J Clin Neurosci, 2009 Apr;16(4):579-81.

PMID: 19201194 DOI: 10.1016/j.jocn.2008.04.029

Neurenteric cysts are rare congenital spinal masses that result from the dysgenesis of the endoderm tissue during development. We report a 4-year-old girl who presented with an insidious onset of lower limb paraparesis. An MRI scan revealed a cervicothoracic intradural extramedullary neurenteric cyst at the thoracic T1/T2 level, with marked spinal cord compression. No associated spinal dysraphism was noted. The patient underwent laminotomy and excision of the cyst. She recovered her neurological functions completely post-operatively, and at her six-month follow-up she was asymptomatic without any neurological deficits. We will discuss the pathogenesis, clinical presentation, and neuroradiological findings. We emphasize the value of early surgical intervention and long-term follow-up when this type of lesion is only partially excised.

Matched MeSH terms: Neural Tube Defects/complications*; Neural Tube Defects/pathology*

Fulltext Red cell folate and predicted neural tube defect rate in three Asian cities

Green TJ, Skeaff CM, Venn BJ, Rockell JE, Todd JM, Khor GL, et al.

Asia Pac J Clin Nutr, 2007;16(2):269-73.

PMID: 17468082

Periconceptional folic acid reduces neural tube defect (NTD) risk. Red blood cell folate concentration is inversely associated with NTD risk. In many countries there is a lack of information on NTD rates. Red cell folate status in women of childbearing age may be a surrogate for NTD rates and may be helpful in identifying countries or regions most likely to benefit from improved folate status.

Matched MeSH terms: Neural Tube Defects/blood; Neural Tube Defects/ethnology; Neural Tube Defects/epidemiology*; Neural Tube Defects/prevention & control

Prenatal detection of birth defects in a Malaysian population: estimation of the influence of termination of pregnancy on birth prevalence in a developing country

Ho JJ, Thong MK, Nurani NK

Aust N Z J Obstet Gynaecol, 2006 Feb;46(1):55-7.

PMID: 16441696

We studied 253 women with a pregnancy complicated by a birth defect and 506 controls to determine the frequency and type of prenatal tests and the types of defects detected antenatally. Most women had at least one ultrasound examination, but the frequency of other screening tests was low. Only 38 (15%) of defects were detected antenatally (37 by ultrasound). Birth prevalence is unlikely to be affected by pregnancy termination.

Matched MeSH terms: Neural Tube Defects/diagnosis; Neural Tube Defects/epidemiology

Rare morbidity of permanent quadriplegia caused by neurenteric cyst of the cervical cord

Tan Chor Lip H, Jih Huei T, Chong Abdullah A, Rahman NABA

Avicenna J Med, 2019 5 31;9(2):78-81.

PMID: 31143701 DOI: 10.4103/ajm.AJM_153_18

The incidence of neurenteric cyst (NC) is rare, accounting for 0.3%-1.3% of all spine tumors. The occurrence of quadriplegia caused by NC is even scarcer. Herein we report on a young girl with a rare NC over the C2-C5 spinal cord, which led to the morbidity of permanent quadriplegia despite early surgical intervention. This case highlights the rare morbidity of cervical cord NC presenting with permanent quadriplegia that failed to respond despite early surgical excision.

Matched MeSH terms: Neural Tube Defects

Fulltext Surgical Management of Large Occipital Encephalocoele: a case report

Sim SK, Theophilus SC, Noor Azman AR

International Medical Journal Malaysia, 2014;13(2):59-62.

MyJurnal

Cranium dysraphism occur less commonly than spinal dysraphism. Overall, occipital encephalocoeles are more frequent than anterior encephalocoes. A large occipital encephalocoele possess difficulty in surgical intervention, not only the sac contains large amount of herniated brain tissue, but the appropriate positioning for successful intubation as well as the higher rate of surgical complications such as cerebrospinal fluid leakage and skin necrosis. In this case report, surgical management of large occipital encephalocoele is discussed. The use of antibiotics in ruptured encephalocoele is recommended.

Matched MeSH terms: Neural Tube Defects

Neural tube defects in Malaysia: data from the Malaysian National Neonatal Registry

Boo NY, Cheah IG, Thong MK, Malaysian National Neonatal Registry

J Trop Pediatr, 2013 Oct;59(5):338-42.

PMID: 23583959 DOI: 10.1093/tropej/fmt026

This study aimed to determine the prevalence and early outcome of neural tube defects (NTDs) in Malaysia. This prospective study included all neonates with NTDs (spina bifida, anencephaly, encephalocoele) born in 2009 in 32 Malaysian hospitals in the Malaysian National Neonatal Network. The prevalence of NTDs was 0.42 per 1000 live births, being highest among the indigenous people of Sarawak (1.09 per 1000 live births) and lowest among Malaysians of Chinese descent (0.09 per 1000 live births). The most common type of NTDs was anencephaly (0.19 per 1000 live births), followed by spina bifida (0.11 per 1000 live births) and encephalocoele (0.07 per 1000 live births). Majority of the infants with anencephaly (94.5%, n = 51), 45.8% (n = 11) with encephalocoele and 9.5% (n = 4) with spina bifida died. The median duration of hospital stay was 4 (range: 0-161) days.

Matched MeSH terms: Neural Tube Defects/epidemiology*

Fulltext MTHFR C677T polymorphism as a risk factor of neural tube defects in Malay: a case control study

Hayati AR, Zainal AI, Tan GC, Ong LC, Khoo TB

Med J Malaysia, 2008 Dec;63(5):379-83.

PMID: 19803295 MyJurnal

Major congenital malformations occur in about 3% of newborn. Several studies have suggested that homozygosity for the C677T methylenetetrahydrofolate reductase (MTHFR) variant is a potential risk factor for neural tube defects (NTDs). It has been hypothesized that the maternal folic acid supplementation prevents NTDs by partially correcting reduced MTHFR activity associated with the variant form of the enzyme. This association has not been found in some ethnic groups. In this study, we attempted to assess the association between NTDs and MTHFR C677T in Malaysian Malay population. Results show that MTHFR 677TT genotype was absent in both patient and control groups.

Matched MeSH terms: Neural Tube Defects/genetics*

Double neural tube defect: a case report and discussions on neural tube development

Vashu R, Liew NS

Childs Nerv Syst, 2010 May;26(5):697-701.

PMID: 20225088 DOI: 10.1007/s00381-010-1093-2

Double neural tube defect is a rare congenital problem. A case illustration and current literatures on neural tube closure theory are discussed. The available theories are summarised and compared with regard to the case report.

Matched MeSH terms: Neural Tube/embryology

Fulltext Acute angle closure glaucoma resulting from myelodysplasia

Ang GS, Tey A, Ng WS, Subrayan V

Med J Malaysia, 2007 Aug;62(3):259-60.

PMID: 18246923

Patients with bleeding diatheses can present in a variety of clinical situations. When these patients manifest with ocular complications, their management can be challenging. We describe a case of acute angle closure glaucoma secondary to subretinal haemorrhage, with myelodysplasia as a predisposing factor.

Matched MeSH terms: Neural Tube Defects/complications*

Fulltext Folic acid in the prevention of neural tube defect--a programme for Malaysia?

Ho JJ

Med J Malaysia, 2004 Mar;59(1):94-9.

PMID: 15535342

There is good evidence that folic acid is safe and efficacious for reducing neural tube defect (NTD). All women capable of becoming pregnant should take 400 microgram daily. This can be given in the form of a daily vitamin supplement, by food fortification, or by increasing natural dietary folates. Compulsory grain fortification has been shown to reduce NTD in a population but supplementation and dietary advice have not. Malaysia should work towards a programme of grain fortification and use alternative strategies to reach sections of the population that would not be covered but several research questions need to be answered before a programme could be implemented in Malaysia.

Matched MeSH terms: Neural Tube Defects/prevention & control*

Amniocentesis for antenatal diagnosis of chromosomal abnormalities and neural tube defects

Singh P

Med J Malaysia, 1979 Jun;33(4):311-6.

PMID: 93235

Matched MeSH terms: Neural Tube Defects/diagnosis*

Predicting Down syndrome and neural tube defects using basic risk factors

Khattak MT, Supriyanto E, Aman MN, Al-Ashwal RH

Med Biol Eng Comput, 2019 Jul;57(7):1417-1424.

PMID: 30877513 DOI: 10.1007/s11517-019-01969-0

Congenital anomalies are not only one of the main killers for infants but also one of the major causes of deaths under 5. Among congenital anomalies, Down syndrome or trisomy 21 (T-21) and neural tube defects (NTDs) are considered the most common. Expectant mothers in developing countries may not have access to or may not afford the advanced prenatal screening tests. To solve this issue, this paper explores the practicality of using only the basic risk factors for developing prediction models as a tool for initial risk assessment. The prediction models are based on logistic regression. The results show that the prediction models do not have a high balanced classification rate. However, these models can still be used as an effective tool for initial risk assessment for T-21 and NTDs by eliminating at least 50% of the cases with no or low risk. Graphical Abstract Prenatal Risk Assessment of Trisomy-21 and Neural Tube Defects.

Matched MeSH terms: Neural Tube Defects/etiology*

Fulltext Cranial neural tube defect after trimethoprim exposure

Abdullah NL, Gunasekaran R, Mohd-Zin SW, Lim BH, Maniam P, Mohd-Salleh AS, et al.

BMC Res Notes, 2018 Jul 16;11(1):475.

PMID: 30012199 DOI: 10.1186/s13104-018-3593-1

OBJECTIVES: The Neural Tube Defects Research Group of University of Malaya was approached to analyze a tablet named TELSE, which may have resulted in a baby born with central nervous system malformation at the University of Malaya Medical Centre. In this animal experimental study, we investigated the content of TELSE and exposure of its contents that resulted in failure of primary neurulation.

RESULTS: Liquid Chromatography Tandem Mass spectrophotometry analysis of the TELSE tablet confirmed the presence of trimethoprim as the active compound. The TELSE tablet-treated females produced significant numbers of embryos with exencephaly (n = 8, 36.4%, *P

Matched MeSH terms: Neural Tube Defects/chemically induced*

Fulltext A rare case of neurenteric cyst of spinal cord with thoracic vertebra fusion successfully managed with spinal cyst excision and posterior instrumentation surgery

Tan Jih Huei, Henry Tan Chor Lip, Chan Chee Kong, Ariz Chong B. Abdullah@Chong Chee Yong, Noor Azman Bin A. Rahman

Malaysian Journal of Medicine and Health Sciences, 2020;16(2):348-350.

MyJurnal

The incidence of neurenteric cyst (NC) is rare amongst spine tumors. It is most often asymptomatic but may present
with sensory and motor symptoms. When associated with thoracic vertebra fusion it is not reported before, this complicates the placement of pedicle screw during posterior instrumentation. Herein, we report a case of thoracic spinal
neurenteric cyst in a 40-year-old man that presents with chronic back pain, left lower limb weakness and numbness.
Elective excision of NC over T6-T7 with laminectomy and multilevel posterior instrumentation was successfully
performed with significant improvement of the symptoms. Neurenteric cyst is a rare spinal cord lesion which may
cause permanent neurological sequalae. Complete surgical excision with spine fixation in this case provides good
long-term outcome.

Matched MeSH terms: Neural Tube Defects

Approaches to deriving Schwann cells from human bone marrow for neural tube regeneration in a clinical setting

Hidayah HN, Mazzre M, Ng AM, Ruszymah BH, Shalimar A

Med J Malaysia, 2008 Jul;63 Suppl A:39-40.

PMID: 19024973

Bone marrow derived Mesenchymal stem cells (MSCs) were evaluated as an alternative source for tissue engineering of peripheral nerves. Human MSCs were subjected to a series of treatment with a reducing agent, retinoic acid and a combination of trophic factors. This treated MSCs differentiated into Schwann cells were characterized in vitro via flow cytometry analysis and immunocytochemically. In contrast to untreated MSCs, differentiated MSCs expressed Schwann cell markers in vitro, as we confirmed by flow cytometry analysis and immunocytochemically. These results suggest that human MSCs can be induced to be a substitute for Schwann cells that may be applied for nerve regeneration since it is difficult to grow Schwann cells in vitro.

Matched MeSH terms: Neural Tube/physiology*

Fulltext Dietary and blood folate status of Malaysian women of childbearing age

Khor GL, Duraisamy G, Loh SP, Green T

Asia Pac J Clin Nutr, 2006;15(3):341-9.

PMID: 16837426

The protective role of folic acid taken during the periconceptual period in reducing the occurrence of neural tube defects (NTD) has been well documented by epidemiological evidence, randomized controlled trials and intervention studies. Much of the evidence is derived from western populations while similar data on Asian subjects is relatively nascent. Baseline data on folate status of Malaysian women is lacking, while NTD prevalence is estimated as 10 per 10,000 births. This study was conducted with the objective of determining the dietary and blood folate status of Malaysian women of childbearing age. A total of 399 women comprising 140 Malay, 131 Chinese and 128 Indian subjects were recruited from universities and worksites in the suburbs of Kuala Lumpur. Inclusion criteria were that the subjects were not pregnant or breastfeeding, not taking folic acid supplements, not habitual drinkers or smokers. Based on a 24-hour recall, the median intake level for folate was 66 microg (15.7-207.8 microg), which amounts to 16.5% of the Malaysian Recommended Nutrient Intakes level. The median (5-95th percentiles) values for plasma and red cell folate (RBC) concentrations were 11 (4-33) nmol/L and 633 (303-1209) nmol/L respectively. Overall, nearly 15.1% showed plasma folate deficiency (< 6.8 nmol/L), with Indian subjects having the highest prevalence (21.5%). Overall prevalence of RBC folate deficiency (<363 nmol/L) was 9.3%, and an almost similar level prevailed for each ethnic group. Only 15.2% had RBC concentration exceeding 906 nmol/L, which is associated with a very low risk of NTD. The result of this study point to the need for intervention strategies to improve the blood folate status of women of childbearing age, so that they have adequate protection against the occurrence of NTD at birth.

Matched MeSH terms: Neural Tube Defects/epidemiology

Fulltext ASPP2 deficiency causes features of 1q41q42 microdeletion syndrome

Zak J, Vives V, Szumska D, Vernet A, Schneider JE, Miller P, et al.

Cell Death Differ, 2016 Dec;23(12):1973-1984.

PMID: 27447114 DOI: 10.1038/cdd.2016.76

Chromosomal abnormalities are implicated in a substantial number of human developmental syndromes, but for many such disorders little is known about the causative genes. The recently described 1q41q42 microdeletion syndrome is characterized by characteristic dysmorphic features, intellectual disability and brain morphological abnormalities, but the precise genetic basis for these abnormalities remains unknown. Here, our detailed analysis of the genetic abnormalities of 1q41q42 microdeletion cases identified TP53BP2, which encodes apoptosis-stimulating protein of p53 2 (ASPP2), as a candidate gene for brain abnormalities. Consistent with this, Trp53bp2-deficient mice show dilation of lateral ventricles resembling the phenotype of 1q41q42 microdeletion patients. Trp53bp2 deficiency causes 100% neonatal lethality in the C57BL/6 background associated with a high incidence of neural tube defects and a range of developmental abnormalities such as congenital heart defects, coloboma, microphthalmia, urogenital and craniofacial abnormalities. Interestingly, abnormalities show a high degree of overlap with 1q41q42 microdeletion-associated abnormalities. These findings identify TP53BP2 as a strong candidate causative gene for central nervous system (CNS) defects in 1q41q42 microdeletion syndrome, and open new avenues for investigation of the mechanisms underlying CNS abnormalities.

Matched MeSH terms: Neural Tube Defects/pathology

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