CMT-CRYAB

CRYAB | 2023

What Is CMT-CRYAB?

CMT-CRYAB is a type of CMT caused by autosomal dominant mutations in the CRYAB gene. This gene provides instructions for making alpha-B-crystallin, a small heat-shock protein that acts as a molecular chaperone, helping other proteins fold correctly and protecting cells, including nerve and muscle cells, from stress. Mutations in the CRYAB gene disrupt this chaperone function, leading to impaired nerve signal transmission.

CMT-CRYAB is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.

Clinical Features

CMT-CRYAB has a late onset, typically after age 40. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.

CMT-CRYAB symptoms may include:

  • Distal weakness in the feet and lower legs, developing after age 40
  • Reduced sensation in the hands and feet
  • Muscle atrophy
  • Foot drop
  • Reduced or absent reflexes
  • Congenital cataracts
  • Breathing muscle weakness is common
  • Additional symptoms not listed here

Disease Course

CMT-CRYAB is slowly progressive following its late onset. Regular cardiac and respiratory monitoring is recommended for affected individuals with this subtype.

Clinical Basics

Subtype
CMT-CRYAB

Classification
Unclassified Subtypes

Neuropathy Type
Axonal

Inheritance Pattern
autosomal dominant

Genetic Context

HGNC-Approved Gene Symbol
CRYAB

Gene Full Name
Crystallin Alpha B

HGNC Gene Alias(es)
CRYA2, HSPB5

Chromosome
11q23.1

Zygosity of Responsible Variant
Heterozygous

Variant Mechanism
Toxic Gain of Function (GoF)

ClinVar Pathogenic Variants

View CMT-CRYAB ClinVar Variants

CRYAB OMIM Entry

CRYAB OMIM

More Info

CMT-CRYAB Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

Mutations in Alpha-B-Crystallin Cause Autosomal Dominant Axonal Charcot-Marie-Tooth Disease with Congenital Cataracts

Authors

Cortese, A., Currò, R., Ronco, R., Blake, J., Rossor, A. M., Bugiardini, E., Laurà, M., Warner, T., Yousry, T., Poh, R., Polke, J., Rebelo, A., Dohrn, M. F., Saporta, M., Houlden, H., Züchner, S., & Reilly, M. M.

Publication Date
September 29, 2023

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

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