Charcot-Marie-Tooth disease type 4B (CMT4B) is a demyelinating autosomal re
cessive motor and sensory neuropathy characterized by focally folded myelin
sheaths in the peripheral nerve, We recently mapped the CMT4B gene to a 5-
cM interval on chromosome 11q22, using homozygosity mapping and haplotype s
haring analysis on a large inbred pedigree, In the present study, we report
the construction of a YAC-based transcript map across the 5-cM critical re
gion, including 26 YACs, 35 STSs, and 52 ESTs. Furthermore, using 15 additi
onal physically ordered microsatellite markers from the 11q22 region on the
original inbred family, we were able to narrow the critical interval for t
he gene to 2 Mb, which is now flanked by markers D11S1757 and CHLC-GATA3B05
. Finally, after computer analysis of the 33 ESTs assigned to the 2-Mb inte
rval, we demonstrated that 21 different transcripts as well as 3 known gene
s might represent potential candidates for the disease. (C) 2000 Academic P
ress.