CMTRID

COX6A1 | 2014

What Is CMTRID?

CMTRID is a type of CMT caused by autosomal recessive mutations in the COX6A1 gene. This gene provides instructions for making a component of the mitochondrial enzyme complex responsible for producing cellular energy. Mutations in the COX6A1 gene disrupt this function, leading to impaired nerve signal transmission.

CMTRID is autosomal recessive, meaning that both copies of the gene must have a mutation to cause this subtype.

Clinical Features

The age of symptom onset in CMTRID is variable, ranging from childhood to adulthood. Symptoms typically begin in the lower extremities and progress over time to involve the upper limbs. Nerve conduction studies usually show somewhat slowed conduction velocities, consistent with an intermediate form of CMT.

CMTRID symptoms may include:

  • Weakness in the feet and lower legs
  • Muscle atrophy
  • Foot drop
  • Reduced or absent reflexes
  • Reduced sensation
  • A steppage-style walking pattern
  • Foot deformities, including high arches, and hammertoes (clawed toes)
  • Progressive involvement of the hands and forearms
  • Difficulty with fine motor skills and manual dexterity
  • Additional symptoms not listed here

Disease Course

CMTRID shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Disease progression is generally slow, and life expectancy is not reduced.

Clinical Basics

Subtype
CMTRID

Classification
CMTRI

Neuropathy Type
Intermediate

Inheritance Pattern
autosomal recessive

Genetic Context

HGNC-Approved Gene Symbol
COX6A1

Gene Full Name
Cytochrome C Oxidase Subunit 6a1

HGNC Gene Alias(es)
COX6AL

Chromosome
12p24.31

Zygosity of Responsible Variant
Homozygous

Mitochondrial Involvement
Yes

Variant Mechanism
Loss of Function (LoF)

ClinVar Pathogenic Variants

View CMTRID ClinVar Variants

CMTRID OMIM Entry

CMTRID OMIM

COX6A1 OMIM Entry

COX6A1 OMIM

More Info

CMTRID Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

A Mutation of COX6A1 Causes a Recessive Axonal or Mixed Form of Charcot-Marie-Tooth Disease

Authors

Tamiya, G., Makino, S., Hayashi, M., Abe, A., Numakura, C., Ueki, M., Tanaka, A., Ito, C., Toshimori, K., Ogawa, N., Terashima, T., Maegawa, H., Yanagisawa, D., Tooyama, I., Tada, M., Onodera, O., & Hayasaka, K.

Publication Date
September 4, 2014

Updated: July 18, 2026 | By: K. Raymond

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