A frameshift mutation in LRSAM1 is responsible for a dominant hereditary polyneuropathy.

Summary: Scientists have solved a genetic mystery within a large family suffering from a hereditary nerve disease known as Charcot-Marie-Tooth (CMT). While many genes are known to cause this condition, the specific cause for this family was unknown until now. By analyzing the DNA of three generations, researchers identified a "frameshift" mutation in a gene called LRSAM1. This gene normally acts as a cellular housekeeper, tagging waste proteins for disposal. The mutation breaks the gene's "machinery," causing waste products (specifically a protein called TSG101) to pile up. When researchers tested this in zebrafish, the fish developed disorganized nerves and movement problems. Crucially, this study proves that LRSAM1 mutations can cause the disease in a "dominant" pattern (inheriting just one bad copy is enough), whereas it was previously only linked to "recessive" forms.