Gamma-S crystallin gene (CRYGS) mutation causes dominant progressive cortical cataract in humans

Sun, Hao; Ma, Zhiwei; Li, Y; Liu, B; Li, Z; Ding, Xing; Gao, Yunyun; Ma, Wenhui; Tang, Xudong; Li, X; Shen, Yifeng

doi:10.1136/jmg.2004.028274

Cited by 78 publications

(45 citation statements)

References 15 publications

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“…In contrast, the Crygs gene belongs from the genetic point of view clearly to the Cryg gene family; however, the biochemical feature (blocked N-terminus) caused its past designation as bs-crystallin [42]. In humans, two CRYGS mutations have been reported resulting in dominant juvenile cataracts, either cortical [43] or progressive [44]. In the mouse, two cataract mutations have been identified in Crygs, Opj (opacity due to poor junctions) as a semi-dominant progressive cataract and a recessive nuclear cataract (allele symbol: rncat).…”

Section: Genes Causing Juvenile Cataractmentioning

confidence: 99%

Clinical and experimental advances in congenital and paediatric cataracts

Churchill

Graw

2011

Phil. Trans. R. Soc. B

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Cataracts (opacities of the lens) are frequent in the elderly, but rare in paediatric practice. Congenital cataracts (in industrialized countries) are mainly caused by mutations affecting lens development. Much of our knowledge about the underlying mechanisms of cataractogenesis has come from the genetic analysis of affected families: there are contributions from genes coding for transcription factors (such as FoxE3, Maf, Pitx3) and structural proteins such as crystallins or connexins. In addition, there are contributions from enzymes affecting sugar pathways (particularly the galactose pathway) and from a quite unexpected area: axon guidance molecules like ephrins and their receptors. Cataractous mouse lenses can be identified easily by visual inspection, and a remarkable number of mutant lines have now been characterized. Generally, most of the mouse mutants show a similar phenotype to their human counterparts; however, there are some remarkable differences. It should be noted that many mutations affect genes that are expressed not only in the lens, but also in tissues and organs outside the eye. There is increasing evidence for pleiotropic effects of these genes, and increasing consideration that cataracts may act as early and readily detectable biomarkers for a number of systemic syndromes.

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Section: Genes Causing Juvenile Cataractmentioning

confidence: 99%

Clinical and experimental advances in congenital and paediatric cataracts

Churchill

Graw

2011

Phil. Trans. R. Soc. B

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“…Maintenance of the structure of one crystallin, cS crystallin, appears to be crucial for long-term transparency of the lens, as two conservative point mutations (Gly-Val) 8 and (Val-Met) 9 have been shown to be responsible for human hereditary cataract. Deamidation of c-crystallins can significantly affect protein structure, 10 and therefore, it is impor-deamidation in the human lens.…”

Section: Introductionmentioning

confidence: 99%

Age‐dependent deamidation of glutamine residues in human γS crystallin: Deamidation and unstructured regions

2012

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Human aging is associated with the deterioration of long-lived proteins. Gradual cumulative modifications to the life-long proteins of the lens may ultimately be responsible for the pronounced alterations to the optical and physical properties that characterize lenses from older people. cS crystallin, a major human lens protein, is known to undergo several age-dependent changes. Using proteomic techniques, a site of deamidation involving glutamine 92 has been characterized and its time course established. The proportion of deamidation increased from birth to teen-age years and then plateaud. Deamidation at this site increased again in the eighth decade of life. There was no significant difference in the extent of deamidation between cataract and age-matched normal lenses. Gln92 is located in the linker region between the two domains, and the introduction of a negative charge at this site may alter the interaction between the two regions of the protein. Gln170, which is located in another unstructured part of cS crystallin, showed a similar deamidation profile to that of Gln92. As the other Gln residues in b-sheet regions of cS crystallin appear to remain as amides, modification of Gln92 and Gln170 thus conforms to a pattern whereby deamidation is localized to the unstructured regions of long-lived proteins.

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“…4 In our study, both the proband and his mother had pulverulent cataract in the center, but with age his mother also had cortical cataract in the periphery, which was not found in the proband. So we speculated that the mutation (G57W) in CRYGS may cause progressive cortical cataract.…”

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confidence: 82%