A NOVEL HOMOZYGOUS MUTATION OF THE MYELIN PO GENE PRODUCING DEJERINE-SOTTAS DISEASE (HEREDITARY MOTOR AND SENSORY NEUROPATHY TYPE-III)

We have previously reported that heterozygosity for myelin Po gene mut ations were associated with Charcot-Marie-Tooth disease type 1B (CMT1B ) or Dejerine-Sottas disease. We investigated the Po gene in a family with clinical Dejerine-Sottas disease and found two children were homo zygous for a deletion of Phe 64. The parents were heterozygous first c ousins with subclinical CMT1B and slow nerve conduction velocities. Th ese results suggest that the effect of homozygous Phe 64 deletion on I mpairment of myelination is dosage-dependent. Clinical phenotype and/o r myelin impairment may be determined both by the type of mutation and by the dosage Of mutated gene. (C) 1996 Academic Press, Inc.