RT Journal Article
SR Electronic
T1 Linkage and mutation analysis in an extended family with Charcot-Marie-Tooth disease type 1B.
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 811
OP 815
DO 10.1136/jmg.31.10.811
VO 31
IS 10
A1 E Nelis
A1 V Timmerman
A1 P De Jonghe
A1 L Muylle
A1 J J Martin
A1 C Van Broeckhoven
YR 1994
UL http://jmg.bmj.com/content/31/10/811.abstract
AB Charcot-Marie-Tooth disease type 1 (CMT1) or hereditary motor and sensory neuropathy type I (HMSNI) is an autosomal dominant peripheral neuropathy. In most families the disease segregates with a 1.5 Mb duplication on chromosome 17p11.2 (CMT1A). A few patients have been found with point mutations in the PMP-22 gene. In some families linkage has been found with markers located on chromosome 1q21-q25 (CMT1B) and more recently mutations have been identified in the P0 gene. We analysed an extended CMT1 pedigree (CMT-B) without the CMT1A duplication. Significant positive linkage with chromosome 1 indicated that this family is of the CMT1B subtype. Sequencing of the candidate gene P0 located in chromosome band 1q21-q23 showed a C to A point mutation at position 446 in exon 3 resulting in an Asp134Glu substitution. Since the P0 mutation cosegregated with CMT1 disease we suggest that this mutation is the primary genetic cause of CMT1B in family CMT-B.