Non-radioactive detection of 17p11.2 duplication in CMT1A: a study of 78 patients.

Abstract

Charcot-Marie-Tooth disease type 1 (CMT1) is a peripheral neuropathy characterised by progressive distal muscular atrophy and sensory loss with markedly decreased nerve conduction velocity, mostly inherited as an autosomal dominant trait. The most common form, type IA, is associated with a 1-5Mb DNA duplication in region pll.2-p12 of chromosome 17 in many patients.In this study a non-radioactive test for detection ofthe CMT1A duplication based on an RM11-GT microsatellite polymorphism is presented. Although different methods have been devised for this purpose, the present method has the advantage of being rapid, informative, economical, easily interpretable, and, therefore, it represents a very useful tool for diagnosis of CMT1A, especially before clear manifestation of clinical symptoms.Seventy-eight patients diagnosed clinically as having CMT and evaluated by electrophysiological methods were tested with an RMII-GT microsatellite and with probe pVAW409R3. The CMT1A duplication was found in 76% of the 56 unrelated patients. RMII-GT was the most informative marker with a heterozygosity of 89%.

Charcot-Marie-Tooth disease type I and related demyelinating neuropathies: Mutation analysis in a large cohort of Italian families

“…In this case, the 17p11.2 duplication was deduced by the presence of either three distinct bands or two bands, one of which exhibits a stronger signal because of its occurrence in two copies. Dosage of alleles was determined by transmission densitometry scanning [Schiavon et al, 1994].…”

Estimation of the Mutation Frequencies in Charcot-Marie-Tooth Disease Type 1 and Hereditary Neuropathy with Liability to Pressure Palsies: A European Collaborative Study

“…ters have been published elsewhere [9,39,[46][47][48][49][50][51][52][53][54]. Only 6 out of 579 (1.0%) patients were found to have a smaller duplication.…”

Charcot-Marie-Tooth Disease in Molise, a Central-Southern Region of Italy: An Epidemiological Study

“…In fact, the duplicated region contains polymorphic markers (RM11GT) consisting of simple repeated sequences (microsatellites) that can be analyzed by means of PCR [11,12]. The presence of 3 distinct alleles or of a difference in intensity (= dosage) between 2 alleles can be easily identified at native polyacrylamide gel electrophoresis followed by highly sensitive silver staining [13].…”