3: GDAP1 MUTATION IN CHARCOT MARIE TOOTH 2K IN THE COLOMBIAN CARIBBEAN AS A CAUSE OF NEUROPATHIC PAIN

Topic: Basic Science
Subtopic: Itch, Genetics and Epigenetics

Background and Aims: The main genes responsible for Charcot-Marie-Tooth type 2 (CMT2) polyneuropathies (axonal) are usually MFN2, GJB, MPZ, GDAP1, HSPB1, and HSPB8, and are a significant cause of neuropathic pain.

Pathogenic and probably pathogenic variants in the heterozygous state of the GDAP1 gene have been associated with CMT2 type 2K with autosomal dominant and recessive inheritance patterns.

In Latin America, we have limited data indicating the presence of mutations in this gene related to CMT2 type 2K.

Methods: We conducted a targeted search of patients with neuropathic pain and suspected hereditary polyneuropathy in the database of the MyoCare institution in Sincelejo, Colombia, who had exome sequencing or NGS results showing a GDAP1 gene mutation, from December 2024 to December 2025.

The results showed the presence of four records with a GDAP1 gene mutation and a clinical and electrophysiological diagnosis of axonal Charcot-Marie-Tooth disease type 2K, who met the criteria for neuropathic pain using the DN4 questionnaire with a score greater than or equal to 4.

Results: The same pathogenic variant was found in the heterozygous state in four patients in the GDPA1 gene on chromosome 8 (8q21.11) c.358C>T p.Arg120Trp. Three (75%) were women and one (25%) was a man. Their ages ranged from 33 to 41 years. Three (75%) were ambulatory and one (25%) was not. Two were in rehabilitation and the other two (50%) were not. The age of onset of symptoms was in the second decade of life in 100% of cases, and all four patients reported having affected family members. All patients experienced burning and prickling sensations, in the lower extremities.

Conclusions: The GDAP1 gene mutation c.358C>T p.Arg120Trp has been found very frequently in the Spanish population of the Mediterranean coast, with a founder effect in this area. The present findings in the Colombian Caribbean population highlight the presence of this mutation in Latin America and the Caribbean as a hidden cause of neuropathic pain with hereditary and genetic characteristics, which we must consider when evaluating patients with CMT2.

References: Pezzini I, Geroldi A, Capponi S, Gulli R, Schenone A, Grandis M, Doria-Lamba L, La Piana C, Cremonte M, Pisciotta C, Nolano M, Manganelli F, Santoro L, Mandich P, Bellone E. GDAP1 mutations in Italian axonal Charcot-Marie-Tooth patients: Phenotypic features and clinical course. Neuromuscul Disord. 2016 Jan;26(1):26-32. doi: 10.1016/j.nmd.2015.09.008. Epub 2015 Sep 16. PMID: 26525999.

Ravanbod M, Mohammadi M, Ghasemi A, Jabbarzadeh S, Okhovat AA, Khani M, Elahi E, Ramezani M, Nafissi S, Alavi A. GDAP1-Related Charcot-Marie-Tooth Disease: Axonal or Demyelinating Subtype? Autosomal Recessive or Autosomal Dominant Inheritance? J Peripher Nerv Syst. 2025 Sep;30(3):e70046. doi: 10.1111/jns.70046. PMID: 40711989.

Presenting Author: Nel Darío Lara Arroyo
Submitting Author: Nel Dario Lara Arroyo

Senior Author: Nel Darío Lara Arroyo

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Carlos Enrique Rangel Gómez: DO - MyoCare Sincelejo
• Maryori Consuelo Amado Suárez: DO - Myocare Sincelejo