We have analyzed a mouse model of Charcot-Marie-Tooth disease 2E (CMT2E) harboring a heterozygous p.Asn98Ser (p.N98S) Nefl mutation, whose human counterpart results in a severe, early-onset neuropathy.
Patients with E90K and N98S frequently presented before age 3 years and developed hearing loss or other neurological features including ataxia and/or cerebellar atrophy on brain MRI.
Patients with E90K and N98S frequently presented before age 3 years and developed hearing loss or other neurological features including ataxia and/or cerebellar atrophy on brain MRI.
Patients with E90K and N98S frequently presented before age 3 years and developed hearing loss or other neurological features including ataxia and/or cerebellar atrophy on brain MRI.
Patients with E90K and N98S frequently presented before age 3 years and developed hearing loss or other neurological features including ataxia and/or cerebellar atrophy on brain MRI.
Patients with E90K and N98S frequently presented before age 3 years and developed hearing loss or other neurological features including ataxia and/or cerebellar atrophy on brain MRI.
We conclude that the NEFL N98S mutation is associated with a DI-CMT phenotype characterized by early-onset sensorimotor neuropathy delaying motor milestones, which may evolve into a severe and complex clinical picture including cerebellar ataxia.
In addition, hNF-L(E397K) developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-L(E397K).
The cellular pathology observed in hNF-L(E397K) mice differed from that recently reported in hNF-L(P22S) mice, suggesting that overt CMT2E phenotypes may arise through different cellular mechanisms.
An investigation to identify the clinical and pathological characteristics of the Pro22Arg revealed that it is associated with demyelinating neuropathy features in CMT1F.
In these sequence variants, 5 variants were polymorphisms, including 3 single nucleotide polymorphisms (SNPs), and 3 other missense mutations (Pro22Thr, Asn97Ser and Ala148Val) were found in the patients with CMT phenotype.