Clinical and Molecular Characterization of Neural Tube Defects with Special Emphasis on MTHFR Gene
Moayad Ahmed MD1, Fawaz Eljili2*, Bashier Mohammed Bashier MD3, Al Sadig Gassoum4 and Sawsan Al Deaf MD3
1Neurosurgeon, Bahri Teaching Hospital, Alia Specialized Hospital, Khartoum, Sudan.
2Neurosurgery Registrar, MRCS, MSc, MPH, Bahri Teaching Hospital, Neurosurgery Department, Khartoum, Sudan.
3Neurosurgeon, National Centre for Neurological Sciences (NCNS), Khartoum, Sudan.
4Research Laboratory, PhD Immunology, National Centre for Neurological Sciences (NCNS), Khartoum, Sudan.
*Corresponding Author: Dr. Fawaz Eljili, Neurosurgery Registrar, MRCS, MSc, MPH, Bahri Teaching Hospital, Neurosurgery Department, Khartoum, Sudan.
Received: August 24, 2022 Published: September 13, 2022
Abstract
Background: Studies have highlighted that MTHFR plays a crucial and essential role in formation of neural tube in early fetal life, and thus occurrence of any mutation to this gene will eventually affected the normal process of neural tube formation leading to defects and the severity of it depends on type of mutation and its impact on clinical picture of patient having this congenital anomalies.
Objectives of the study: To describe demographic data and clinical presentation of Sudanese patients with neural tube defect. To characterize MTHFR gene in Sudanese patients with neural tube defects. To correlate clinical presentation with molecular findings of MEHFR gene.
Material and methods: This is a cross-sectional study that had been performed at National Center of Neurological Sciences (NCNS) during June 2016 to October 2019. The study included clinical data and peripheral blood sample taken from all neural tube defects patients diagnosed at NCNS, during the above mention period. The study was conducted in accordance with the guidelines of the local ethical committee. Blood samples were obtained from 50 neural tube defect patients. Blood samples were taken in sterile containers that contained EDTA and processed for DNA extraction. The extracted DNA was amplified by PCR for detection of MTHFR gene.
Results: A total of 50 patients were studied, the linguistic affiliation of the studied patients showed that neural tube defects were common in Afro Asiatic tribes’ mothers 42% and were 38% Nilo-Saharan. The common mother age group was 21-25 years 52%, followed by 31-35 years 34%. The clinical presentation regarding deficit was not favorable because 80 % of patients were having variable degrees of neurological deficits. The sequence results showed that, Insertion A was detected in one sample (lumber myelomeningocele) at 3 positions cDNA.113_114insA (ch1:11863189_11863190insT), cDNA.114_115insA (1:11863190_11863191insT) and cDNA.115_116insA (1:11863191_11863192insT) consecutively. Insertion A at those positions was at 5’UTR regions and changes were set as splice site changes. A>G was found in the same previous sample at position cDNA.92A>G (chr1:11863211T>C) and was predicted as polymorphism change at 5’UTR region a splice site change. A>T was detected in the same sample in position cDNA 1559A>T (ch1:11854064) resulting in polymorphism and amino acids sequence change at the CDS region. C>T was elicited in sample of patient with sacral meningiocele at position cDNA 246 (ch1:11863057) at CDS region resulting in polymorphism splice site change. rs (2066470) no amino acid changes.
Conclusion: In conclusion this study showed that female predominates and constitutes 60% of affected patient. The most common type of open neural tube defects was meningiomyelocele forming 88% of all affected patients and the most common site was Lumbo-sacral region. Strong correlation was detected between anatomical site and motor deficit, 34 patients with lumbo-sacarl myelomeningocele were having neurological deficit in form of bilateral lower limb weakness. The sequence results in this study showed that, Insertion A was detected in one sample in 3 positions and A>G was found and predicted as polymorphism change at 5’UTR region a splice site change, also A>T was detected in same sample resulting in polymorphism and amino acids sequence change at the CDS region. C>T was elicited in another sample at position cDNA 246, at CDS region resulting in polymorphism splice site change, with no amino acid changes.
Keywords: MTHFR Gene, Molecular characterization, Neural tube defects
Citation: Ahmed M, Eljili F, Bashier BM, Al Sadig G, Al Deaf S. “Clinical and Molecular Characterization of Neural Tube Defects with Special Emphasis on MTHFR Gene”. SVOA Neurology 2022, 3:5, 176-196.
