What are the genetic changes related to spinal muscular atrophy with respiratory distress type 1 ?
Mutations in the IGHMBP2 gene cause SMARD1. The IGHMBP2 gene provides instructions for making a protein involved in copying (replicating) DNA; producing RNA, a chemical cousin of DNA; and producing proteins. IGHMBP2 gene mutations that cause SMARD1 lead to the production of a protein with reduced ability to aid in DNA replication and the production of RNA and proteins. These problems particularly affect alpha-motor neurons, which are specialized cells in the brainstem and spinal cord that control muscle movements. Although the mechanism is unknown, altered IGHMBP2 proteins contribute to the damage of these neurons and their death over time. The cumulative death of alpha-motor neurons leads to breathing problems and progressive muscle weakness in children with SMARD1.  Research suggests that the amount of functional protein that is produced from the mutated IGHMBP2 gene may play a role in the severity of SMARD1. Individuals who have some functional protein are more likely to develop signs and symptoms later in childhood and retain a greater level of muscle function.