Marked phenotypic variation in a family with a new myelin protein zero mutation

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Neuromuscul Disord. 2005 Sep 27

Marked phenotypic variation in a family with a new myelin protein

zero mutation.

Szabo A, Zuchner S, Siska E, Mechler F, Molnar MJ.

Department of Neurology, University Medical School of Debrecen,

Debrecen, Hungary.

Myelin protein zero (MPZ) is a member of the immunoglobulin gene

superfamily, which has a role in myelin compaction. MPZ gene

mutations cause mostly demyelinating neuropathies of the Charcot-

Marie-Tooth 1B type (CMT1B), but axonal CMT have been described as

well. There is a broad spectrum of phenotypic manifestation of

neuropathies caused by MPZ mutations. Some mutations of MPZ cause

severe early-onset neuropathies such as Dejerine-Sottas disease,

while others cause the classical CMT phenotype with normal early

milestones but development of disability during the first two decades

of life. We describe a family in which five members of three

consecutive generations had a heterozygous mutation in nucleotide

position 143 with a T-C transition in exon 2 of the MPZ gene. The

resulting substitution of Leu48 with proline has not been previously

described. The age of onset of symptoms varied from 8 months to 41

years. The marked variation of the age of disease onset and clinical

phenotype in this one family, related to the same MPZ mutation,

suggests that in addition to the type and intragenic location of the

mutation, other putative modifying gene(s) are regulating MPZ gene

expression, mRNA stability and posttranslational protein modification

and may have an important effect on the ultimate clinical phenotype.