Researchers in Spain Identify 2 Most Common GDAP1 Gene Mutations that Lead to CMT

Researchers in Spain conducted a large study to investigate the incidence of GDAP1 gene mutations leading to Charcot-Marie-Tooth disease (CMT).

The study provided useful information on the most common mutations occurring in this gene and the clinical profile associated with each of them. It was published in the journal Scientific Reports and titled, “Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain.”

Mutations in the GDAP1 gene — which encodes a protein that contributes to energy production in cells — lead to the development of CMT. According to researchers, mutations in this gene are quite rare in most Western countries but not in certain regions of Spain or other Mediterranean countries.

“In Spain, the relative frequency of GDAP1 mutations has been reported to be as high as 13% of the genetically defined CMT in certain regions,” researchers wrote. “This contrasts with the scarcity of these mutations in most Western Countries, accounting for less than 2% of the genetically defined patients in series from the United Kingdom, Germany, [and the] United States. …”

To investigate the clinical and genetic profile of these mutations in Spain, researchers analyzed all CMT patients from 14 centers across the country from 2000 to 2016. Their ages ranged from 3–79, and 99 had GDAP1 mutations. These patients lived across most of Spain, but particularly in the northwestern and Mediterranean regions.

Further analysis found two main types of GDAP1 mutations: p.R120W and p.Q163X. The severity of disease in patients with the p.R120W mutation varied, and 29% had no symptoms at all (called asymptomatic patients). This mutation was detected mostly in the Mediterranean coast.

Patients with the p.Q163X mutation, however, had a more severe form of the disease and presented certain symptoms, such as dysphonia (difficulty in producing vocal sounds) and respiratory anomalies. This mutation was especially detected in the north and northwest of Spain.

“This is the largest clinical series of CMT patients with GDAP1 mutations and it contributes to expand the knowledge of the genetic distribution and genotype-phenotype correlation [the relationship between genetic patterns and observable characteristics of a condition] of this disease,” the researchers concluded.

CMT is a group of inherited disorders that affect the peripheral motor nerves of the body, which control muscle contractions, movement, and other activities involving muscles, such as speaking, breathing, and swallowing. Symptoms include muscle weakness, abnormal gait, and foot deformities. According to the Charcot-Marie-Tooth Association, CMT is estimated to affect about 2.8 million people worldwide.