Disease relevance of CRYBB2

• Mutation analysis of congenital cataracts in Indian families: identification of SNPS and a new causative allele in CRYBB2 gene [1].
• The t(11;22)(p15.5;q11.23) in a retroperitoneal rhabdoid tumor also includes a regional deletion distal to CRYBB2 on 22q [2].
• METHODS: After confirming the presence of significant post-bypass coagulopathy, patients undergoing repair of congenital heart defects using cardiopulmonary bypass were randomised to the use of BP (group BP) or no intervention (group C) [3].
• Epistemic analysis was conducted by determining the degree of confidence associated with the selected models, which was found to be 50%/50% (E-1pop/BP) for low and moderately pathogenic Salmonella strains, and 9.8%/90.2% (E-2pop/BP) for highly virulent strains [4].

High impact information on CRYBB2

• A CA-repeat polymorphism at the CRYB2 locus was the most informative marker in our families (lod score 5.99), but because the observed recombination fraction between NF2 and CRYB2 was 10 cM, predictions using this marker will need to be interpreted with caution [5].
• Here we report that a chain-termination mutation in CRYBB2 is associated with ADCC in this family [6].
• Earlier studies from our laboratory showed that a secreted binding protein for fibroblast growth factors (BP) is expressed at high levels in SCC cell lines and tissue samples [7].
• We conclude that retinoids down-regulate BP gene expression by post-transcriptional as well as by transcriptional mechanisms [7].
• In six different human SCC cell lines, we found that all-trans-retinoic acid (tRA) down-regulated BP mRNA by 39-89% within 24 h [7].

Biological context of CRYBB2

• We report linkage in this family to the region on chromosome 22q that includes two beta crystallin genes (CRYBB2, CRYBB3) and one pseudogene (CRYBB2P1) [8].
• However, a substitution (W151C in exon 6 of CRYBB2) was identified as the most likely causative mutation underlying the phenotype of central nuclear cataract in all affected members of family C176 [1].
• CONCLUSIONS: Exon 6 of CRYBB2 appears to be a critical region susceptible for mutations leading to lens opacity [1].
• Genetic heterogeneity of the Coppock-like cataract: a mutation in CRYBB2 on chromosome 22q11.2 [9].
• RESULTS: Several single nucleotide polymorphisms in CRYG, CRYBB2, and GJA8 genes were observed [1].

Anatomical context of CRYBB2

• From this group of cell lines, we selected the ME-180 cell line for more detailed studies of the mechanisms of this regulation. tRA down-regulated BP mRNA in a time- and dose-dependent manner [7].
• Comparison of Western ligand blots of neonatal serum, BRL-3A conditioned media, rat amniotic fluid, and rat cerebrospinal fluid (CSF) demonstrated that all contained a prominent 28 K BP [10].
• In the present study, we show by different experimental approaches that human eosinophils can express Mac-2/epsilon BP [11].
• Macrophage cell-surface protein 2 (Mac-2), a galactose specific S-type lectin identified in inflammatory macrophages, presents a high degree of homology with the rat IgE-binding protein (epsilon BP) [11].
• After lysis of the erythrocytes, noncovalently bound BP and its metabolites were effectively removed from hemoglobin under mild conditions by using hydrophobic interaction and size-exclusion liquid chromatography [12].

Associations of CRYBB2 with chemical compounds

• Actinomycin D and cycloheximide blocked the tRA effect, suggesting that transcriptional regulation as well as de novo protein synthesis contribute to this post-transcriptional regulation of BP mRNA levels [7].
• Strict control of BP and protein excretion rate, lowering of blood lipids, tight glucose control for individuals with diabetes, and lifestyle changes form part of the future multimodal protocol for treatment of patients with chronic nephropathies [13].
• Finally, human epsilon BP was purified from several human cell lines and shown to possess lactose-binding characteristics and cross-species reactivity to murine IgE [14].
• During five 2-day phases, ten normal volunteers randomly received three times daily with standardized meals aluminum hydroxide alone and concurrently with NaHCO3, calcium acetate, CCA, or with CCA 2 hours postprandially [15].
• A significant decrease in systolic and diastolic 24-h blood pressure (24 hBP) and daytime BP (dtBP) was achieved with the combination of ACEI and NAC (ACEI + NAC) when compared to the period with only ACEI: 24 hBP = 146.1 +/- 4.2 vs 137 +/- 3.1 (p < 0.05) and 89.2 +/- 2.8 vs 83.5 +/- 3.7mmHg (p = 0.01) [16].

Other interactions of CRYBB2

• Moreover, the D22S258, CRYBA4, D22S300, D22S1, and D22S310 loci, which lie between CRYBB2 and D22S42, were found to be deleted, presumably as a result of the translocation event [2].
• Eleven C. capucinus chromosomes are homologous to 11 human chromosomes: CCA 2 = HSA 4; CCA 3 = HSA 6; CCA 12 = HSA 9; CCA 16 = HSA 11; CCA 10 = HSA 12; CCA 11 = HSA 13; CCA 20 = HSA 17; CCA 8 = HSA 19; CCA 23 = HSA 20; CCA 24 = HSA 22; and CCA X = HSA X [17].
• RESULTS: Sequencing of the coding regions and flanking intronic sequences of CRYBB2 and CRYBB1 showed the presence of a novel, heterozygous X253R change in exon 6 of CRYBB1 [18].
• These DNA markers (CRYB2, NEFH, D22S268, and D22S280) can also be used for presymptomatic diagnosis in other NF2 families [19].
• The region between the beta B2-1 crystallin locus (CRYB2A) and the myoglobin locus (MB) was commonly deleted in these tumors [20].

Analytical, diagnostic and therapeutic context of CRYBB2

• METHODS: Nine Indian families, clinically documented to have congenital/childhood cataracts, were screened for mutations in candidate genes such as CRYG (A-->D), CRYBB2, and GJA8 by PCR analyses and sequencing [1].
• Gel filtration of digested peptide demonstrated the action of an endopeptidase capable of hydrolyzing BP peptide 43-88 into large fragments [21].
• Northern blot performed with eosinophil RNA hybridized with the human Mac-2 or epsilon BP cDNA probes revealed that eosinophils presented a unique transcript at 1.2 kb [11].

References