Student Saint Louis University belleville, Illinois, United States
Abstract Body : INTRODUCTION: Spina bifida (SB) is the most common congenital malformation of the central nervous system (CNS) and occurs as a result of the disruption of primary neurulation with myelomeningocele being the most severe form. SB can be associated with hydrocephalus, Arnold Chiari malformation, bowel and bladder dysfunction, lower limb paralysis, and pain syndromes. Despite many studies suggesting possible causes such as folic acid deficiency, genetic disorders, cohort factors and maternal health characteristics, the mechanism of SB is still unclear. To address such shortcomings, a thorough dissection and genetic sequencing analysis was performed on a cadaveric body of the individual with SB.
METHODS: The body of a 55-year-old female was received through the Gift Body Program of Saint Louis University (SLU) with signed informed consent from the donor. The reported medical history included surgical correction of open SB, urinary diversion (Kock pouch), kidney disease, hydrocephalus, seizures, and opioid dependence. Routine dissection was performed following standard human gross anatomy dissection protocols. The whole exome sequencing (WES) of cadaveric DNA was performed on Illumina Next Generation Sequencing platform.
RESULTS: The donor presented with noticeable short stature and atypically small hands and feet. During dissection of the vertebral column, neither a conus medullaris nor cauda equina were identifiable, similar to a tethered cord, and the spinal cord was observed descending into the sacral canal. Evidence of a Kock pouch was observed as an abnormal appearance of the ileocecal junction. The bioinformatics analysis of WES data yielded 86 rare (minor allele frequency, MAF ≤ 0.01) pathologic/deleterious genetic variants, none of which have been previously linked to SB. The functional annotation of these variants pointed toward the polygenic underlining of the present case.
CONCLUSION: The current case provides important novel information on the molecular mechanism(s) of CNS congenital malformation(s).
FUNDING: Provided by Center for Anatomical Science and Education (CASE), SLU School of Medicine
