CRYAB Gene Chromosomal Locus
The CRYAB gene (encoding alpha-B crystallin) is located at chromosomal locus 11q22.3-q23.1. 1
Gene Location and Structure
- The CRYAB gene maps to the long arm of chromosome 11, specifically at bands q22.3 to q23.1 1
- The genomic sequence spans 3,189 base pairs and contains three exons separated by two introns 2
- The open reading frame consists of 528 base pairs encoding a protein of 175 amino acids 2
Clinical Significance of CRYAB Mutations
- Mutations in CRYAB cause myofibrillar myopathy (MFM), which can present with dilated, hypertrophic, or restrictive cardiomyopathy 3
- The gene is inherited in an autosomal recessive pattern, unlike most other MFM-associated genes which follow autosomal dominant inheritance 3
- Childhood-onset disease has been described for CRYAB mutations, with rapid progression leading to severe cardiomyopathy that may precede skeletal muscle involvement 3
- Cardiac manifestations include sinus node dysfunction, atrioventricular block, supraventricular and ventricular tachycardias, heart failure, and sudden death 3
Protein Function
- Alpha-B crystallin is a member of the small heat shock protein family that functions as a molecular chaperone to prevent protein aggregation under stress conditions 1
- The protein is abundantly expressed in lens, cardiac muscle, and skeletal muscle, where it maintains cytoskeletal integrity by chaperoning desmin and vimentin 3
- CRYAB mutations activate NFKB-dependent autophagy at the cellular level 3