Charcot-Marie-Tooth disease type 1A: a family study with microsatellites

Charcot-Marie-Tooth (CMT) disease (also called Hereditary Motor and Sensory Neuropathy) is an inherited peripheral neuropathy with a prevalence rate of 1 in 2,500. Charcot-Marie-Tooth disease type 1A (CMT1A), the most common autosomal dominant form of the disease, is associated with a duplication of a segment of chromosome 17 (17p11.2). In this report we present a three-generation family with CMT1A where simple sequence repeats (di- or tri-nucleotide repeats, also called microsatellites) were used in conjunction with polymerase chain reaction (PCR) to identify the duplication. The presence of three alleles or the presence of two alleles with a dosage ratio of 1:2 for the markers D17S839 and D17S921 indicates the presence of the duplicated segment in affected family members, whereas two alleles with a ratio of 1:1 indicate absence of the duplication. Several markers outside the duplication region which have two alleles with a dosage ratio of 1:1 were used as controls. Seven CMT1A patients in this family carry the CMT1A duplication. One 12-year-old boy who has not exhibited any clinical symptoms does not have the CMT1A duplication. We believe that this is a simple, rapid, and effective method to identify the CMT1A duplication in most patients suspected of having CMT1A.