Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type spondylometaphyseal dysplasia

Sedaghatian-type spondylometaphyseal dysplasia is a rare syndrome characterized by abnormal bone development with shortened limbs and flattened spine.  Affected children also have heart rhythm defects and brain abnormalities such that they pass away shortly after birth.  Eighteen infants affected with this rare disease have been reported worldwide.  We studied two families and identified loss-of-function mutations in the gene GPX4, a member of the glutathione peroxidase family of antioxidant defense enzymes that protects cells against cell death and lipid peroxidation.  Our findings highlight the importance of proper functioning of this enzyme in development of the cardiac, nervous and skeletal systems. (By Dr. Kym Boycott, http://jmg.bmj.com/content/early/2014/04/04/jmedgenet-2013-102218 )