Capillary electrophoresis for the detection of PMP22 gene duplication: Study in

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Electrophoresis. 2008 Mar 3 [Epub ahead of print]

Capillary electrophoresis for the detection of PMP22 gene

duplication: Study in Mexican patients.

Hernández-Zamora E, de la Luz Arenas-Sordo M, Maldonado-Rodríguez R.

Genetics Department, Instituto Nacional de Rehabilitación, México

City.

Charcot-Marie-Tooth (CMT) disease is the most common inherited

disorder of the human peripheral nerve, with an estimated overall

prevalence of 17-40/10 000 [1]. The typical phenotype presents

peroneal muscular atrophy and pes cavus [2]. CMT is usually divided

into two large types, about two-thirds of the patients have CMT type

1 (CMT1), that affects the layer of myelin (demyelination). In type 2

(CMT2) the nerve fibers are affected (axonal). CMT diseases have

autosomal dominant, autosomal recessive, and X-linked inheritance

[1].

The most frequent subtype is 1A (CMT1A) with autosomal dominant

transmission, secondary in most cases to a tandem duplication of a

1.5 Mb DNA fragment on chromosome 17p11.2-p12 [4-7]. In this region,

the codification of the peripheral myelin protein 22 (PMP22) takes

place.

The severity of the disease varies among patients, even within the

same family, from almost no symptoms to severe foot-drop and sensory

loss. The PMP22 gene has four exons and is regulated by two promoters

located toward the extreme 5'. The origin of the duplication that

causes the disease is an uneven exchange of the chromatids during the

meiosis.

This unequal recombination occurs between two regions that limit the

PMP22 gene, described as REP places of 24 kb, proximal and distal [3,

4].