Genetic Research and CMT 1A Update from Spain

[Guest guest]

Abstract on CMT 1A and Genetic Research from Spain

1: Rev Neurol 2002 Aug 1;35(3):246-53

[Advances in the molecular genetics of the hereditary neuropathies]

[Article in Spanish]

Palau ez F, Cuesta Peredo A, Pedrola Vidal L.

Institut de Biomedicina de Valencia (CSIC), Valencia, Espa a.

OBJECTIVE. We reviewed current knowledge of the molecular and genetic

bases of hereditary peripheral neuropathies, with special emphasis on

the senso motor neuropathies and their different clinical phenotypes.

DEVELOPMENT. The peripheral neuropathies show great clinical variability

and genetic heterogeneity. To date 12 genes and over 20 genetic loci

have been described in relation to Charcot Marie Tooth disease and

related neuropathies. The commonest form is the type 1A Charcot Marie

Tooth disease (CMT1A) caused by tandem duplication of a monomer of 1.5

megabases (Mb) on chromosome 17q11.2. The CMT 1A duplication is found in

70% of the patients with CMT 1. The deletion of 1.5 Mb is the most

prevalent mutation (85%) in hereditary neuropathy with susceptibility to

paralysis due to pressure. This monomer includes the PMP22 gene which is

affected by a genetic dose effect. The different proteins encoded by the

genes described are well expressed in the Schwann cell and in the nerve

axon. They have different functions. There are the structural proteins

of myelin,

transcription factors, cytoskeleton components, molecular motors of the

microtubules, proteins involved in growth and cellular differentiation

or with

presumed enzyme activity. CONCLUSIONS. Diagnosis of molecular pathology

is important for genetic counselling. The development of new treatment

for hereditary neuropathies is based on the generation of animal models

for the different genes and on understanding the role of the proteins

involved in axon Schwann cell interaction.