Mapping of a new locus for autosomal recessive demyelinating Charcot-Marie-Tooth disease to 19q13.1-13.3 in a large consanguineous Lebanese family: Exclusion of MAG as a candidate gene

Autosomal recessive Charcot-Marie-Tooth disease (CMT) type 4 (CMT4) is a co mplex group of demyelinating hereditary motor and sensory neuropathies pres enting genetic heterogeneity. Five different subtypes that correspond to si x different chromosomal locations have been described. We hereby report a l arge inbred Lebanese family affected with autosomal recessive CMT4, in whom we have excluded linkage to the already-known Loci. The results of a genom ewide search demonstrated linkage to a locus on chromosome 19q13.1-13.3, ov er an 8.5-cM interval between markers D19S220 and D19S412, A maximum pairwi se LOD score of 5.37 for marker D19S420, at recombination fraction [theta]. 00, and a multipoint LOD score of 10.3 for marker D19S881, at theta =.00, s trongly supported linkage to this locus. Clinical features and the results of histopathologic studies confirm that the disease affecting this family c onstitutes a previously unknown demyelinating autosomal recessive CMT subty pe known as "CMT4F." The myelin-associated glycoprotein (MAG) gene, located on 19q13.1 and specifically expressed in the CNS and the peripheral nervou s system, was ruled out as being the gene responsible for this form of CMT.