PDXK-Related Neuropathy: A Case With a Novel Splice-Altering Missense Variant and Literature Review

Area of Science:

• Genetics
• Neurology

Background:

• PDXK-related neuropathy is a rare hereditary motor and sensory neuropathy.
• It is caused by variants in the PDXK gene and can be treated with pyridoxal 5'-phosphate supplementation.

Purpose of the Study:

• To report a novel PDXK variant and investigate its functional impact.
• To explore the disease mechanism of PDXK-related neuropathy.

Main Methods:

• Whole-exome sequencing was performed on a patient with neuropathy.
• Functional studies were conducted using patient-derived RNA to analyze gene variant effects.

Main Results:

• A novel missense variant (c.826G>C, p.(Ala276Pro)) in the PDXK gene was identified in a patient.
• This variant was predicted to disrupt splicing, confirmed by functional studies, leading to aberrant transcript degradation.
• The patient presented with peripheral neuropathy but lacked optic atrophy, possibly due to age.

Conclusions:

• A novel splice-altering missense variant in PDXK was identified, revealing a new disease mechanism.
• This finding contributes to understanding PDXK-related neuropathy and its genetic basis.