A family with axonal sensorimotor polyneuropathy with TUBB3 mutation

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Mutations in the β‑tubulin isotype III (TUBB3) gene are linked to TUBB3 syndrome, encompassing congenital fibrosis of the extraocular muscle type 3 (CFEOM3), intellectual disability, and axonal sensorimotor neuropathy.
• The clinical spectrum of TUBB3 mutations exhibits significant variability, including differences in disease onset and progression.

Purpose of the Study:

• To investigate the role of a specific TUBB3 mutation (D417N) in a family presenting with axonal sensorimotor polyneuropathy.
• To explore the relationship between TUBB3 mutations and the clinical heterogeneity observed in peripheral neuropathies.

Main Methods:

• Whole exome sequencing to identify genetic mutations.
• Clinical assessment of patients, including neurological examination and gait analysis.
• Sural nerve biopsy to examine nerve pathology.

Main Results:

• A TUBB3 D417N mutation was identified in a family with axonal sensorimotor polyneuropathy.
• Patients presented with progressive gait disturbance but lacked ophthalmoplegia and intellectual impairment, indicating axonal peripheral neuropathy without CFEOM3.
• Sural nerve biopsy revealed an absence of large myelinated fibers, consistent with axonal loss.

Conclusions:

• Specific TUBB3 mutations, such as D417N, can predominantly cause axonal peripheral neuropathy, independent of CFEOM3.
• TUBB3 mutations play a role in modulating the inter- and intra-familial heterogeneity of clinical phenotypes in neurological disorders.