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.
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
-
Complex
Details
Mechanistic basis:
Mixed
Confidence:
Low
Prediction:
The literature predicts a complex mechanism for CMT-CRYAB: αB-crystallin is an obligate oligomeric chaperone, so the dominant alleles are predicted to both co-assemble into and disrupt wild-type αB and αA-crystallin complexes (a dominant-negative effect) and lose chaperone activity (a partial loss), alongside any neomorphic aggregation. Because the widely cited Arg120Gly toxic-aggregation account is drawn from dominant myofibrillar myopathy rather than this subtype's own alleles, confidence stays low until CMT-CRYAB-specific variants are characterized.
Rationale:
Because αB-crystallin assembles as an obligate oligomer, mutant subunits are predicted to co-assemble into and disrupt wild-type αB and αA-crystallin complexes and to lose chaperone activity, a mixed dominant-negative and partial-loss picture alongside any neomorphic aggregation. The toxic-aggregation account is imported from dominant myofibrillar myopathy rather than characterized from this subtype's own alleles, so confidence stays low.
Updated: July 18, 2026 | By: K. Raymond
