LOCALIZATION OF A GENE RESPONSIBLE FOR AUTOSOMAL RECESSIVE DEMYELINATING NEUROPATHY WITH FOCALLY FOLDED MYELIN SHEATHS TO CHROMOSOME 11Q23 BY HOMOZYGOSITY MAPPING AND HAPLOTYPE SHARING

Hereditary motor and sensory neuropathy (HMSN) with focally folded mye lin sheaths, or Charcot-Marie-Tooth type 4B (CMT4B), is a distinct cli nical entity belonging to the heterogeneous group of autosomal recessi ve demyelinating neuropathies. We first described a large pedigree wit h CMT4B, which showed a high consanguinity level and an autosomal rece ssive pattern of inheritance, Through conventional linkage analysis, w e excluded linkage of the locus segregating in this pedigree to any of the known genes responsible for other HMSNs. Using homozygosity mappi ng and haplotype sharing analysis, we were able to localize the diseas e gene in a 4 cM interval on chromosome 11q23, between the D11S1332 an d D11S917 loci. On the basis of the clinical characteristics of the di sease, we propose that this locus corresponds to the CMT4B gene.