Novel mutation of the P-0 extracellular domain causes a Dejerine-Sottas syndrome

A patient is described with a Dejerine-Sottas syndrome caused by a novel he terozygous Cys (98) Tyr mutation in the extracellular domain of the major p eripheral myelin protein zero (P(0)ex). Homotypical interactions between P( 0)ex tetramers of apposed extracellular faces of the Schwann cell membrane play a crucial part in myelin compaction. The amino acid change disrupts a unique disulphide bond that stabilises the immunoglobulin-like structure of P(0)ex and it is predicted to cause severe dehypomyelination through domin ant negative effects on the wild type protein.