Spinal Muscular Atrophy with Respiratory Distress (SMARD1): Mutational Analysis

Investigator:

• Iris L. Gonzalez, PhD
  

Background

The genetic disease SMARD1 (SMA with Respiratory Distress) was previously thought to be a more severe variant of a disease called SMA (Spinal Muscular Atrophy). Both of these diseases involve loss of motor nerve cells in the spinal cord and the resulting symptoms are progressive muscle weakness and wasting. In both SMA and SMARD1, the muscles responsible for breathing can be involved and the severity of breathing impairment can vary broadly and can be quite severe. Unfortunately, there is no easy way to distinguish these two diseases.

Children with SMA have mutations in a gene called SMN, which stands for Spinal Motor Neuron. Recent work has shown that the more severe SMARD1 is actually a separate disease caused by mutations in another gene called IGHMBP2. We are looking at mutations in both the SMN and IGHMBP2 genes to try and distinguish SMA from SMARD1, and we are working to develop and implement a test for SMARD1. This test is currently not available in the US.

What We're Doing

A strategy for amplifying the IGHMBP2 gene and performing DNA sequencing is being implemented. We are testing 14 patients who likely have mutations in this gene and are comparing their DNA sequences with the normal reference sequence.

Some of What We've Found

Many normal variants of the IGHMBP2 gene are known and we have detected some of these. At the same time, we have detected some changes that might be damaging to proper functioning of the gene and may be the cause of disease in the subjects tested. When the information has been completed, we will compare our set to the compilation of variants of the German group that discovered this gene.