MPAN can also be inherited in an autosomal dominant manner
The NBIA research group of Dr. Susan Hayflick at Oregon Health & Science University in Portland (OR, USA) has discovered that mitochondrial membrane protein-associated neurodegeneration (MPAN) can also be inherited in an autosomal dominant manner. MPAN is one of the four most common NBIA variants and is caused by mutations in the gene C19orf12. Until now, it was assumed that the disease is inherited exclusively in an autosomal recessive manner. This means that there must be 2 mutations to trigger the disease, one each from the father and the mother. In a new publication, however, Hayflick and her team show that there are also a number of MPAN patients in whom a mutation alone can trigger the disease with the symptoms typical of MPAN. It was also possible to detect isolated mutations that were not inherited but had new occurrences in the patients, so-called de novo mutations.
Implications for diagnostics and genetic counseling
These research findings have implications for the diagnosis and genetic counseling of MPAN patients and their families. If a single MPAN mutation is detected in a patient with clinical symptoms of MPAN, the treating physician must consider autosomal dominant MPAN in the differential diagnosis. According to the authors of the article, the respective genotype can often provide information about whether a single mutation is sufficient to trigger the disease. Since MPAN can only occur in adulthood, the latest findings are of considerable importance for those affected by dominant MPAN. Your children are at increased risk of developing the disease as well.
Bibliographic information for the article:
Gregory A, Lotia M, Jeong SY, Fox R, Zhen D, Sanford L, Hamada J,
Jahic A, Beetz C, Freed A, Kurian MA, Cullup T, van der Weijden MCM, Nguyen V, Setthavongsack N, Garcia D, Krajbich V, Pham T, Woltjer R, George BP, Minks KQ, Paciorkowski AR, Hogarth P, Jankovic J, Hayflick SJ. Autosomal dominant mitochondrial membrane protein-associated neurodegeneration (MPAN). Mol Genet Genomic Med. 2019 May 13;:e736.
Here is the link to the Pubmed abstract:
https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&dopt=Abstract&db=PubMed&list_uids=31087512
Here is the link to the full article:
https://onlinelibrary.wiley.com/doi/full/10.1002/mgg3.736
