HGNC Approved Gene Symbol: CRYBB1
Cytogenetic location: 22q12.1 Genomic coordinates (GRCh38): 22:26,599,278-26,618,027 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 22q12.1 | Cataract 17, multiple types | 611544 | Autosomal dominant; Autosomal recessive | 3 |
Den Dunnen et al. (1986) cloned and characterized the rat beta-crystallin-B1 gene. The predicted protein contains 247 amino acids and is about 55% similar to the bovine homolog (den Dunnen et al., 1985).
Hulsebos et al. (1995) mapped the human and mouse crystallin beta-B1 genes. PCR primers were designed based on the previously reported rat sequence. The human gene was localized in the region 22q11.2-q12.1 using a somatic cell hybrid DNA panel that included characterized deletions of that chromosome. The mouse homolog was mapped to the central part of chromosome 5 using interspecific backcross analysis. In both species this crystallin is linked to other members of the family, including CRYBA4 (123631), CRYBB2 (123620), and CRYBB3 (123630).
Stempel et al. (2003) identified beta B1-crystallin as a new cytoplasmic ciliary body antigenic target of perinuclear anti-neutrophil cytoplasmic antibody. This characterization of beta B1-crystallin outside the lens raised questions about its extralenticular expression, intracellular role, and potential target of inflammation in uveitis.
In a family with autosomal dominant pulverulent cataract mapping to chromosome 12q11.2 (CTRCT17; 611544), Mackay et al. (2002) sequenced the CRYBB1 gene and detected a G-to-T transversion in exon 6 that cosegregated with cataract in the family. This single-nucleotide change was predicted to introduce a translation stop codon at glycine 220 (G220X; 600929.0001).
In a large 3-generation family from the UK with autosomal dominant congenital cataract and microcornea, Willoughby et al. (2005) identified heterozygosity for an X253R substitution (600929.0003) that segregated fully with disease and was not found in controls.
In 2 unrelated consanguineous inbred Bedouin families from southern Israel presenting with autosomal recessive congenital nuclear cataract, Cohen et al. (2007) identified an identical homozygous deletion mutation (168delG; 600929.0002) in the CRYBB1 gene in affected individuals of both families.
In a 5-generation Chinese family with autosomal dominant congenital cataract and microcornea, Wang et al. (2011) identified a missense mutation in the CRYBB1 gene (S129R; 600929.0004) that segregated fully with disease in the family and was not found in controls.
In all 8 affected members in 4 generations of a family with pulverulent cataract (CTRCT17; 611544), Mackay et al. (2002) demonstrated heterozygosity for a G-to-T transversion in exon 6 of the CRYBB2 gene, resulting in a gly220-to-stop (G220X) nonsense mutation. Expression of recombinant human CRYBB1 in bacteria showed that the truncated G220X mutant was significantly less soluble than wildtype. The cataract was bilateral in all cases and consisted of fine, dust-like opacities that affected mainly the central zone, or fetal nucleus, of the lens but also affected the cortex and the anterior and posterior Y-suture regions. Opacities were present from birth. There was no family history of other ocular or systemic abnormalities.
In affected members of 2 unrelated consanguineous Bedouin families segregating autosomal recessive congenital nuclear cataract (CTRCT17; 611544), Cohen et al. (2007) identified homozygosity for a 1-bp deletion (168delG) in exon 2 of the CRYBB1 gene, resulting in a frameshift at amino acid 57 and premature termination at amino acid 107. The parents of those affected were heterozygous for the mutation, which was not found in 100 unrelated Bedouin control individuals.
In affected members of a large 3-generation family from the UK with autosomal dominant congenital cataract and microcornea (CTRCT17; 611544), Willoughby et al. (2005) identified heterozygosity for a c.827T-C transition (c.827T-C, NM_001887) in exon 6 of the CRYBB1 gene, resulting in a ter253-to-arg (X253R) substitution at a highly conserved residue. The mutation was predicted to cause translational read-through and elongation of the COOH-terminal chain by an additional 26 amino acid residues. The mutation segregated fully with disease in the family and was not found in 190 ethnically matched controls.
In a 5-generation Chinese family with autosomal dominant congenital cataract and microcornea (CTRCT17; 611544), Wang et al. (2011) identified a c.387C-A transversion (c.387C-A, NM_001887.3) in exon 4 of the CRYBB1 gene, resulting in a ser129-to-arg (S129R) substitution. The mutation segregated fully with disease in the family and was not found in 100 controls. Analysis of biophysical properties of recombinant beta-crystallins revealed that S129R impaired the structures of both the beta-B1-crystallin homomer and the beta-B1/beta-A3-crystallin heteromer. In addition, the mutation significantly decreased the thermal stability of the beta-B1/beta-A3-crystallin but not beta-B1-crystallin.
Cohen, D., Bar-Yosef, U., Levy, J., Gradstein, L., Belfair, N., Ofir, R., Joshua, S., Lifshitz, T., Carmi, R., Birk, O. S. Homozygous CRYBB1 deletion mutation underlies autosomal recessive congenital cataract. Invest. Ophthal. Vis. Sci. 48: 2208-2213, 2007. [PubMed: 17460281] [Full Text: https://doi.org/10.1167/iovs.06-1019]
den Dunnen, J. T., Moormann, R. J. M., Lubsen, N. H., Schoenmakers, J. G. G. Intron insertions and deletions in the beta/gamma-crystallin gene family: the rat beta-B1 gene. Proc. Nat. Acad. Sci. 83: 2855-2859, 1986. [PubMed: 3458246] [Full Text: https://doi.org/10.1073/pnas.83.9.2855]
den Dunnen, J. T., Moormann, R. J. M., Schoenmakers, J. G. G. Rat lens beta-crystallins are internally duplicated and homologous to gamma-crystallins. Biochem. Biophys. Acta 824: 295-303, 1985. [PubMed: 3879970] [Full Text: https://doi.org/10.1016/0167-4781(85)90035-1]
Hulsebos, T. J. M., Gilbert, D. J., Delattre, O., Smink, L. J., Dunham, I., Westerveld, A., Thomas, G., Jenkins, N. A., Copeland, N. G. Assignment of the beta-B1 crystallin gene (CRYBB1) to human chromosome 22 and mouse chromosome 5. Genomics 29: 712-718, 1995. [PubMed: 8575764] [Full Text: https://doi.org/10.1006/geno.1995.9947]
Mackay, D. S., Boskovska, O. B., Knopf, H. L. S., Lampi, K. J., Shiels, A. A nonsense mutation in CRYBB1 associated with autosomal dominant cataract linked to human chromosome 22q. Am. J. Hum. Genet. 71: 1216-1221, 2002. [PubMed: 12360425] [Full Text: https://doi.org/10.1086/344212]
Stempel, D., Sandusky, H., Lampi, K., Cilluffo, M., Horwitz, J., Braun, J., Goodglick, L., Gordon, L. K. Beta B1-crystallin: identification of a candidate ciliary body uveitis antigen. Invest. Ophthal. Vis. Sci. 44: 203-209, 2003. [PubMed: 12506076] [Full Text: https://doi.org/10.1167/iovs.01-1261]
Wang, K. J., Wang, S., Cao, N.-Q., Yan, Y.-B., Zhu, S. Q. A novel mutation in CRYBB1 associated with congenital cataract-microcornea syndrome: the p.Ser129Arg mutation destabilizes the beta-B1/beta-A3-crystallin heteromer but not the beta-B1-crystallin homomer. Hum. Mutat. 32: E2050-E2060, 2011. Note: Electronic Article. [PubMed: 21972112] [Full Text: https://doi.org/10.1002/humu.21436]
Willoughby, C. E., Shafiq, A., Ferrini, W., Chan, L. L. Y., Billingsley, G., Priston, M., Mok, C., Chandna, A., Kaye, S., Heon, E. CRYBB1 mutation associated with congenital cataract and microcornea. Molec. Vision 11: 587-593, 2005. [PubMed: 16110300]