DE-NOVO MUTATION OF THE MYELIN P(O) GENE IN DEJERINE-SOTTAS DISEASE (HEREDITARY MOTOR AND SENSORY NEUROPATHY TYPE-III)

We have investigated the myelin P(o) gene on chromosome 1 as a candida te gene in two sporadic cases with Dejerine-Sottas disease or heredita ry motor and sensory neuropathy (HMSN) type III. We found different mu tations, a cysteine substitution for serine 63 in the extracellular do main and an arginine substitution for glycine 167 in the transmembrane domain. The patients were genetically heterozygous for the normal all ele and the mutant allele, which was absent in their parents and in on e hundred unrelated, healthy controls. The results strongly suggest th at a de novo dominant mutation of the P(o) gene is responsible for at least some sporadic cases of Dejerine-Sottas disease.