Hi Teresa,
I have 3 mutant genes, two of which encode proteins that are located in the mitochondria. The first is SDHB Ile127Ser, c. 380 T>G, which means that at position 127 of the protein, the Isoleucine amino acid has been replaced with the Serine amino acid. This is a pathogenic, i.e., disease causing mutation. The protein is located in the respiratory chain of the mitochondria inner membrane, and it is one of a chain of proteins responsible for producing ATP from food. The second mutant gene is FBXL4 Cys547fs*, c. 1641_1642, which means that at position 127 of the protein, there has been a frame shift mutation, so everything downstream in the protein is incorrect and the protein most likely terminates early. This is pathogenic as well. FBXL4 is important for fusion of mitochondrion to form more productive mitochondria, and it also regulates the degradation and recycling of defective mitochondria via lysosomes. I am heterozygous (one good copy, one bad copy) for each of these genes and both of my mutations is recessive for mitochondrial dysfunction. I've been told that I have only half the amount of normal SDHB and FBXL4, which means that my mitochondria aren't functioning at full capacity. (If I was homozygous for either of these two genes, i.e., it would be fatal in infancy). So, it is the combination of the two proteins, each operating at 50% capacity, that is likely causing mito dysfunction and neuropathy, along with a number of other symptoms. These two mutant proteins cause over time damage to the mitochondria, so that the mitos eventually are degraded by lysosomes. Ultimately, this can produce mitochondrial depletion which means symptoms including neuropathy, chronic fatigue, GI issues, etc. which vary from one person to the next. If your doctors suspect mitochondrial myopathy, genetic testing is important. To cover all the bases, they may do whole genome sequencing or if they are looking for suspected culprit mutant genes, they may only do a panel. Re the neuroendocrine tumors, these potentially could be caused by mutant SDHB. SDHB Ile127Ser is dominant for tumors/cancers, and I've read that there's about a 20% chance of developing a tumor if you're a carrier. I had one at age 9; it was not cancerous and never recurred. So it's my mutant SDHB that gave rise to the NET, and the combination of my mutant FBXL4 and SDHB that likely is responsible for mitochondrial dysfunction and neuropathy. (It's strange, but true, that mutant SDHB is dominant for tumors, but recessive for mitochondrial dysfunction.) There are 100s or 1000s of other genes that encode mitochondrial proteins, and if mutant, might cause mitochondrial dysfunction. I would appreciate learning from you how it turns out with Univ Michigan. Best of luck!