A second locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 19q13.3

Autosomal recessive Charcot-Marie-Tooth disease (CMT) represents a heteroge neous group of disorders affecting the peripheral nervous system. The axona l form of the disease is designated as "CMT type 2" (CMT2), and one locus ( 1q21.2-q21.3) has been reported for the autosomal recessive form. Here we r eport the results of a genomewide search in an inbred Costa Rican family (C R-I) affected with autosomal recessive CMT2. By analyzing three branches of the family we detected linkage to the 19q13.3 region, and subsequent homoz ygosity mapping defined shared haplotypes between markers D13S902 and D19S9 07 in a 5.5-cM range. A maximum two-point LOD score of 9.08 was obtained fo r marker D19S867, at a recombination fraction of .00, which strongly suppor ts linkage to this locus. The epithelial membrane protein 3 gene, encoding a PMP22 homologous protein and located on 19q13.3, was ruled out as being r esponsible for this form of CMT. The age at onset of chronic symmetric sens ory-motor polyneuropathy was 28-42 years (mean 33.8 years); the electrophys iological data clearly reflect an axonal degenerative process. The phenotyp e and locus are different from those of demyelinating CMT4F, recently mappe d to 19q13.1-13.3; hence, the disease affecting the Costa Rican family cons titutes an axonal, autosomal recessive CMT subtype (ARCMT2B).