RAPID SCREENING OF MYELIN GENES IN CMT1 PATIENTS BY SSCP ANALYSIS - IDENTIFICATION OF NEW MUTATIONS AND POLYMORPHISMS IN THE P-0 GENE

Charcot-Marie-Tooth type 1 (CMT1) disease or hereditary motor and sens ory neuropathy type I (HMSNI) is an autosomal dominant peripheral neur opathy. In most CMT1 families, the disease cosegregates with a 1.5-Mb duplication on chromosome 17p11.2 (CMT1A). A few patients have been fo und with mutations in the peripheral myelin protein 22 (PMP-22) gene l ocated in the CMT1A region. In other families mutations have been iden tified in the major peripheral myelin protein P-0 gene localized on ch romosome 1q21-q23 (CMT1B). We performed a rapid mutation screening of the PMP-22 and P-0 genes in non-duplicated CMT1 patients by single-str and conformation polymorphism analysis followed by direct polymerase c hain reaction sequencing of ge nomic DNA. Six new single base changes in the P-0 gene were observed: two missense mutations in, respectively , exons 2 and 3, two nonsense mutations in exon 4, and two silent muta tions or polymorphisms in, respectively, exons 3 and 6.