A mendelian form of neural tube defect caused by a de novo null variant in SMARCC1 in an identical twin

  • Ann Neurol. 2018 Feb;83(2):433-436. doi: 10.1002/ana.25152.
Fuad Al Mutairi  1  2 ,  Fatema Alzahrani  3 ,  Farouq Ababneh  1 ,  Amna A Kashgari  4 ,  Fowzan S Alkuraya  3  5  6
Affiliations
  • 1. Medical Genetic Division, Department of Pediatrics, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
  • 2. King Abdullah International Medical Research Centre, King Saud Bin Abdulaziz, University for Health Sciences, Riyadh, Saudi Arabia.
  • 3. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • 4. Medical Imaging Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
  • 5. Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
  • 6. Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
PMID: 29360170 DOI: 10.1002/ana.25152
Abstract

Neural tube defects (NTDs) are among the most common birth defects in humans and yet their molecular etiology remains poorly understood. NTDs are believed to result from the complex interaction of environmental factors with a multitude of genetic risk factors in a classical multifactorial disease model. Mendelian forms of NTDs in which single variants are sufficient to cause the disease are extremely rare. We report a monozygotic twin with severe NTDs (occipital encephalocele and myelomeningocele) and a shared de novo, likely truncating, variant in SMARCC1. RTPCR analysis suggests the potential null nature of the variant attributed to nonsense-mediated decay. SMARCC1 is extremely constrained in humans and encodes a highly conserved core chromatin remodeler, BAF155. Mice that are heterozygous for a null allele or homozygous for a hypomorphic allele develop severe NTDs in the form of exencephaly. This is the first report of SMARCC1 mutation in humans, and it shows a critical and conserved requirement for intact BAF chromatin remodeling complex in neurulation. Ann Neurol 2018;83:433-436.