Krzysztof Piotrowski
DIAGEN Co., Poland
Title: The genetic background of human neural tube development: Quest to a personalized prophylaxis
Biography
Biography: Krzysztof Piotrowski
Abstract
Congenital Neural Tube Defects (NTDs) are common malformations both as an isolated form and a part of genetic syndromes. Extraordinarily fast development of molecular genetics confi rms that almost all NTDs are genetically dependent in terms of aberrations in diff erent regions of a chromosome or single gene mutations. On the other hand, NTDs are an important component of diverse genetic diseases, including monogenic and metabolic disorders with mutations (oft en called polymorphism) genes responsible for the condition of the MTHFR gene. Th e genes participating therein are located nearly on each chromosome, mainly on pathways, along with ligand genes and co-factors, transcription factors or individually. Many mechanisms on NT development are based on the balance between apoptosis, proliferation and migration. Crucial genes controlling fetal development, including the creation of neural tube and the forming of vertebral continuity are primary “homeobox” genes grouped in 4 clusters HOX1-4. Other genes condition the forming of diff erent structures. Th e most important pathways are Shh, Wnt, FGF, Notch and BMP. Th ese pathways are closely connected with other structures of the body like conus heart, thymus, intestinal tract and skin or symphatic nervous system. The most complicated is closing of column. On the one hand, this process does not depend on one but on numerous genes, especially Pax3, Pax7 and on the other hand, it depends on proper work mainly of Folic Acid Path, as well as Vitamin B12 and Choline. However, it is of great importance to know the real FA level, which is not refl ected in the serum. Neural development is also aff ected by the imprinting (about 30 genes) and the inactivation of the X chromosome in day 21st of embryo development. In our daily prenatal practice we are able to fi nd specifi c NTDs as soon as 12th week of gestation but our target is to confi rm if NTDs may be of truly isolated nature or non-specifi c mild ultrasound co-markers. As you can see above, we have a lot of information and we can prevent many open NTDs, but still aff ected children are born. It means that our knowledge about it is not yet complete. Presently, we have some possibilities to help the baby in uterus to close peripheral open NT if it’s not too big and has isolated nature.