Myelomeningocele is the most serious type of spina bifida and the most common structural congenital defect of the central nervous system. A study has identified a genetic mutation that leads to the risk of this diseaseas published this Thursday Science.
Spina bifida is a type of neural tube defect (the structure of an embryo that will become the brain, spinal cord, and surrounding tissues), which occurs when fetal spine does not close completely during the first month of pregnancy.
Myelomeningocele (MM) can give rise to various physical and developmental difficultiesand although its incidence has decreased in recent decades, largely thanks to folic acid fortification, it remains a problem in some areas of the world.
The causes of MM remain largely unknown and the risk attributable to common genetic variants remains unexplored. The study now published has been prepared by an international group called the Spina Bifida Sequencing Consortium.
22.98 times more likely
Exome (a part of the genome) and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal deletions (a missing or deleted chromosome) 22q11.2.
This suggests that patients with MM would have 22.98 times more likely to host 22q11.2 deletion compared to the general population, as summarized Science.
According to the results, this risk is mediated by the loss of Crkl, one of the genes that express neural tube located in the 22q11.2 deletion interval, and this risk is only partially alleviated with folic acid supplementation.
Analysis of genetic data from a separate cohort of individuals with 22q11.2 deletion suggested that the risk of MM was approximately 12 to 15 times higher than expected.
Using a mouse modelthe authors investigated candidate genes driving MM risk and found that loss of Crkl was sufficient to reproduce a neural tube defect in those animals.
The team noted that the common 22q11.2 deletion confers a substantial risk of myelomeningocele, “partially alleviated by folic acid supplementation.”
