Charcot-Marie-Tooth disease: a novel Tyr145Ser mutation in the myelin protein zero (MPZ, P0) gene causes different phenotypes in homozygous and heterozygous carriers within one family


Charcot-Marie-Tooth disease type 1B (CMT 1B) is caused by mutations in the gene coding for peripheral myelin protein zero (MPZ, P0) that plays a fundamental role in adhesion and compaction of peripheral myelin. Here we report a Costa Rican family with a hereditary peripheral neuropathy due to a novel Tyr145Ser MPZ mutation. Four family members were heterozygously affected; two siblings of two heterozygous carriers were homozygous for this mutation. On neurological examination the heterozygous parents and their homozygous children both showed distal sensory deficits. The mother and the siblings displayed impaired deep tendon reflexes and mild sensory ataxia. The homozygous individuals were more severely affected with an earlier age of onset, distal motor weakness, and pupillary abnormalities. Electrophysiological studies revealed both signs of demyelination and axonal nerve degeneration. The sural nerve biopsy of one sibling showed thinly myelinated nerve fibers, onion bulb formation, and clusters of regenerating fibers. On electron microscopy axonal degeneration and decompaction of inner myelin layers were found. This Costa Rican family shows phenotypic variability depending on the homozygous or heterozygous state of the Tyr145Ser mutation carriers.

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We thank the family members who collaborated in this study for giving their informed consent, blood samples, and the biopsy. Support form the Vicerrectoría de Investigación, University of Costa Rica is gratefully acknowledged (project 742-98-241). A.L. is a recipient of a scholarship from the Deutscher Akademischer Austauschdienst. This study was supported by the Deutsche Forschungsgemeinschaft and Deutsche Gesellschaft für Muskelkranke (DGM, AFM) (to B.R.) and by the ELAN funds (to D.H.). All experiments performed comply with current laws in Costa Rica and Germany.

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Correspondence to Bernd Rautenstrauss.

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A. Leal and C. Berghoff contributed equally to this work.

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Leal, A., Berghoff, C., Berghoff, M. et al. Charcot-Marie-Tooth disease: a novel Tyr145Ser mutation in the myelin protein zero (MPZ, P0) gene causes different phenotypes in homozygous and heterozygous carriers within one family. Neurogenetics 4, 191–197 (2003).

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  • MPZ, P0
  • CMT1B
  • HMSN1B
  • Charcot-Marie-Tooth disease