Sci Adv: Researchers have identified new genetic disorders that affect the brain and skull bones

January 22, 2021 /--- Researchers at the National Institutes of Health have discovered a new genetic disorder characterized by delayed development and deformities in the brain, heart and facial features.
, known as linked defect syndrome (LINKED), is caused by a mutation in the OTUD5 gene that interferes with key molecular steps in embryonic development.
that newly discovered molecular mechanisms may be critical to human development.
information will help scientists better understand common and rare diseases and improve patient care.
results were published in the January 20, 2021 issue of Science Advance.
(Photo: www.pixabay.com) The project began with a study of boys born with severe birth defects, including abnormalities in the brain, skull bones, heart and urinary tract, by Dr. Dan Kastner, a clinical researcher at the National Human Genome Institute's (NHGRI) laboratory.
an in-depth examination of the genomes of siblings and their family members, together with genetic bio-informational analysis, found that mutations in the OUD5 gene may have been the cause of the disease.
contact with other researchers who studied similar problems, Baker found seven other men between the ages of 1 and 14 who shared symptoms with the first patient and had different mutations in the OUD5 gene.
the gene contains instructions for the manufacture of the OTUD5 enzyme, which is associated with ubibinization, a process in which proteins are molecularly altered to alter their function.
plays an important role in regulating the fate of cells, indicating that stem cells become specific cell types in the early stages of embryonic development.
based on genetic evidence, I'm pretty sure that the OUD5 mutation causes the disease, but I don't know how this enzyme causes symptoms in our patients after the mutation," Beck said.
, we are looking to work with Dr. Werner's team, which specializes in biochemical methods to understand the function of enzymes such as OUD5.
, the NIH team examined cells taken from patient samples that were processed at the NIH Clinical Center.
by using a method to restore mature human cells to embryonic stem cell-like states, scientists have found that the OUD5 mutation is associated with abnormal nerve cell development.
further experiments, the team found that OUD5 enzymes act on protein substrates called chromatin remodelers.
these proteins physically alter the tightly wrapped DNA strands in the nucleals of cells, making certain genes easier to open or express.
the researchers concluded that OTUD5 usually prevents these chromosomal remodelers from being labeled as destructive.
, however, when OTUD5 mutates, its protective function is lost and chromatin remodelers are destroyed, leading to abnormal development of neuroplates and nerve cells.
, these changes can lead to some birth defects in LINKED patients.
(Bioon.com) Source: Researchers identify new genetic disorder that affects brain, craniofacial skeleton Original source: Beck D.B., Basar M.A., et al. Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation. Science Advances. Jan 20, 2021. DOI: 10.1126/sciadv.abe2116