CMT 2 and DSS: Two novel missense mutations in the myelin protein zero gene cau

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BMC Res Notes. 2010 Apr 12;3(1):99.

Two novel missense mutations in the myelin protein zero gene causes

Charcot-Marie-Tooth type 2 and Dejerine-Sottas syndrome.

Braathen GJ, Sand JC, MB.

ABSTRACT: BACKGROUND: The Charcot-Marie-Tooth (CMT) phenotype caused by mutation

in the myelin protein zero (MPZ) gene varies considerably, from early onset and

severe forms to late onset and milder forms. The mechanism is not well

understood. The myelin protein zero (P0) mediates adhesion in the spiral wraps

of the Schwann cell's myelin sheath. The crystalline structure of the

extracellular domain of the myelin protein zero (P0ex) is known, while the

transmembrane and intracellular structure is unknown.

FINDINGS: One novel missense mutation caused a milder late onset CMT type 2,

while the second missense mutation caused a severe early onset phenotype

compatible with Dejerine-Sottas syndrome.

CONCLUSIONS: The phenotypic variation caused by different missense mutations in

the MPZ gene is likely caused by different conformational changes of the MPZ

protein which affects the functional tetramers. Severe changes of the MPZ

protein cause dysfunctional tetramers and predominantly uncompacted myelin, i.e.

the severe phenotypes congenital hypomyelinating neuropathy and Dejerine-Sottas

syndrome, while milder changes cause the phenotypes CMT type 1 and 2.