Disease relevance of CRYAB

• The current study extends those findings to the following crystallin genes involved in some congenital cataracts: CRYAA (R116C), CRYAB (R120G), and CRYGC (T5P) [1].
• In contrast, another CRYAB mutation, Arg120Gly, reported in desmin-related myopathy decreased the binding to both N2B and striated muscle-specific I26/27 domains and showed intracellular aggregates of the mutant protein [2].
• Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing [3].
• CRYAB promoter polymorphisms: influence on multiple sclerosis susceptibility and clinical presentation [4].

High impact information on CRYAB

• We identified an R120G missense mutation in CRYAB that co-segregates with the disease phenotype in this family [5].
• Muscle cell lines transfected with the mutant CRYAB cDNA showed intracellular aggregates that contain both desmin and alphaB-crystallin as observed in muscle fibers from DRM patients [5].
• This region contains the alphaB-crystallin gene (CRYAB), a candidate gene encoding a 20-kD protein that is abundant in lens and is also present in a number of non-ocular tissues, including cardiac and skeletal muscle [5].
• 3. The maximum LOD score, 3.92 at recombination fraction 0, was obtained for marker D11S898, near the gene that encodes crystallin alpha-B protein (CRYAB) [6].
• In contrast, the other sHsp Hsp27/HspB1 and alphaB-crystallin/HspB5 had no effect [7].

Biological context of CRYAB

• Direct DNA sequence of CRYAB revealed a heterozygous C-->T transition at nucleotide 58, resulting in a novel 58 C-->T (Pro20Ser) mutation [8].
• Single-strand conformation polymorphism (SSCP) analysis for exon 1 of CRYAB was performed in all family members and 200 normal control subjects [8].
• In addition, CRYAB gene promoter methylation seems to occur in distinct ATCs [3].
• Consistent and marked downregulation of TFCP2L1 was identified as one of the main mechanisms contributing to CRYAB gene silencing in ATCs [3].
• RESULTS: In CRYAB (Genbank ) no mutations were found but SNPs were identified in the promoter region (g.CRYAB-249C>G, g.CRYAB-650C>G and g.CRYAB-652A>G), and intronic region (g.CRYAB.2398T>G) [4].

Anatomical context of CRYAB

• In order to map sequences corresponding to clone 6.2 and to physically define the boundaries of the localization of CRYA2, we used somatic cell hybrids carrying either different human chromosomes or Chr 11 segments and a cell line established from a patient with an interstitial deletion of region 11q14.3-q22 [9].
• There was selective expression in paraffin-embedded sections of alpha B-crystallin (CRYA2) in oligodendroglia in all areas of the nervous system examined. alpha B-Crystallin is a major optic lens protein but also a heat shock protein and molecular chaperone found in brain and a number of other tissues [10].

Regulatory relationships of CRYAB

• RESULTS: The CRYAB polymorphisms influenced susceptibility as well as disease expression in MS [11].

Other interactions of CRYAB

• As MPP1 and CRYAB are also among the 14 genes differentially expressed in all three of the drug-resistant sublines, they represent the strongest candidates for resistance against DNA-damaging drugs [12].
• Both CRYAB and TNFAIP1 show increased transcript levels in AD brains, supporting the validity of this approach [13].
• To explore the novel disease gene for DCM, we examined CRYAB encoding alphaB-crystallin for mutation in the patients with DCM, since alphaB-crystallin was recently reported to associate with the heart-specific N2B domain and adjacent I26/I27 domain of titin/connectin, and we previously reported a N2B mutation, Gln4053ter, in DCM [2].
• Importantly, low expression of two products, the lysosomal protease CTSD and the lens crystallin CRYAB, was significantly associated with adverse patient survival [14].
• METHOD: CRYAB was screened for mutations in 233 MS patients and 96 controls [4].

Analytical, diagnostic and therapeutic context of CRYAB

• Candidate genes [DES and alphaB-crystallin (CRYAB)] were screened using sequence analysis [15].
• CRYA2 has previously been mapped to 11q22.3-23.1 by in situ hybridization [9].

References