DE-NOVO MUTATION (AG-98-]CYS) OF THE MYELIN P-0 GENE AND UNCOMPACTIONOF THE MAJOR DENSE LINE OF THE MYELIN SHEATH IN A SEVERE VARIANT OF CHARCOT-MARIE-TOOTH-DISEASE TYPE 1B

A point mutation (Arg(98)-->Cys) of exon 3 coding for the extracellula r domain of the myelin protein zero (P-0) gene was found in a sporadic case of an eighteen year old Japanese man with a severe variant of Ch arcot-Marie-Tooth disease type 1B (CMT1B). A de novo mutation was esta blished by parentage testing and analyses of the P, gene in the family . This patient showed delayed motor development, nonprogressive limb w eakness and kyphoscoliosis. In addition to the nerve biopsy findings t ypical of CMT1B, such as segmental demyelination, marked decrease in t he density of myelinated fibers, and frequent onion-bulb formation, ul trastructural examination disclosed uncompaction of the major dense li nes with slight widening of the intraperiod distance in the inner laye rs of the myelin sheath. Although mutations in the extracellular domai n of P-0 should affect hemophilic adhesion between external surfaces o f Schwann cell processes, resulting in the separation at the intraperi od lines, our study shows uncompacted major dense lines as a main myel in abnormality where the cytoplasmic domain of P-0 resides. (C) 1997 E lsevier Science B.V.