These patients were negative for pathogenic variants of PMP22
, MFN2, MPZ, GJB1, GDAP1, HSPB1, HSPB8, EGR2, NEFL , and RAB7 .
In mid-90s researchers executed the expansive dispensation of PMP22
ribonucleic acid (RNA) in various mesodermal and ectodermal tissues of growing mice also in the villi of the matured gut indicating a broader biologic importance for PMP22
in cell multiplication or specialisation.
Although the common disease-causing genes PMP22
and MPZ were not mutated in this case, the diagnosis is probably CMT1, because of the clinical and neurophysiological findings of demyelinating sensorimotor neuropathy in the patient and his mother.
However, hypertelorism could also be attributed to the involvement of contiguous genes or to mutations in genes distinct from PMP22
These sequences were less similar to human plasmolipin than the corresponding frog and pufferfish MAL and PMP22
proteins were to human counterparts (Table 1).
Candidate genes are going to be tested according to the phenotype; the duplication in chromosome 17, and mutations in PMP22
, Cx32 and MPZ, as well as in other genes will be searched.
In this study, using targeted next-generation sequencing (NGS) technology, we identified a novel PMP22
missense mutation in an autosomal dominant demyelinating CMT family.
A specific example would be testing first for PMP22
duplications and deletions in a patient with neuropathy and an appropriate clinical presentation, before proceeding with testing for less prevalent mutations that can also cause hereditary neuropathy.
We also analyzed 50 patients with hereditary neuropathy with liability to pressure palsies (HNPP), who were hemizygous for the PMP22
region (34), as confirmed by the observation of a deletion-specific junction fragment obtained with probe pNEA102.
The gene encoding peripheral myelin protein 22 (PMP22
) maps in this interval, and several lines of evidence have indicated that alterations in gene dosage of PMP22
are responsible for the pathogenesis of CMT1A [reviewed in Refs.
Although mutations within the PMP22
gene have been identified in some cases of CMT1A and HNPP, a gene dosage effect has been proposed as the principal underlying pathomechanism for development of CMT1A and HNPP (9-11).
the number of copies of a gene per somatic cell) of the PMP22
gene, a myelin gene involved in inherited neuropathies (1).