Phenotypic variation of a new P0 mutation in genetically identical twins

Abstract

We have identified a new point mutation in the myelin protein zero (P0) gene in two genetically identical twins with a demyelinating neuropathy. The G to A transition at nucleotide position 382 caused an aspartic acid to asparagine substitution in exon 3. Moreover, we found clear clinical differences which were most evident at an early age. These observations suggest that the expression of this P0 mutation may be susceptible to external, non-genetic influences that may act early in the course of the disease to alter the phenotype.

Increased gene dosage of myelin protein zero causes Charcot‐Marie‐Tooth disease

“…Intrafamilial phenotypic variability has also been reported in patients with MPZ nucleotide substitutions. 19,20 To investigate whether there are correlations between the expression levels of MPZ and phenotypic variability, we performed quantitative analysis of MPZ mRNAs in lymphoblastoid cell lines of the affected patients. However, there were no obvious relationships between them.…”

A novel point mutation in PMP22 gene associated with a familial case of Charcot-Marie-Tooth disease type 1A with sensorineural deafness

“…This phenomenon may, of course, be attributed to the time of diagnosis and symptom severity. But several reports [12,13] have documented possible anticipation in CMT and deafness, although the exact mechanism for this pattern has not been elucidated.…”

Peripheral neuropathies caused by mutations in the myelin protein zero

“…Several affected members of this family developed proximal as well as distal leg weakness, and also developed large and small fiber sensory loss prior to adolescence [45]. Only one patient developed what ultimately was characterized as a mild neuropathy [48]. Virtually, all the early onset cases were areflexic in childhood.…”