A CRYBB2 mutation in a Taiwanese family with autosomal dominant cataract

Ching, Yung-Hao; Yeh, Jih‐I; Fan, Wen‐Lang; Chen, Ko-Chen; Yeh, Man-Chieh; Woon, Peng Yeong; Lee, Yuan‐Chieh

doi:10.1016/j.jfma.2018.01.005

Cited by 4 publications

(5 citation statements)

References 19 publications

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“…Multiple studies have revealed that CRYBB2 gene mutations (including p.Q155X [17][18][19], p.E167X [20]) were associated with congenital autosomal dominant cataracts. In our study, we also found a CRYBB2 novel mutation (p.Gly161Arg) in simply microphthalmos eyes in Family 2.…”

Section: Discussionmentioning

confidence: 99%

Three novel mutations of microphthalmos identified in two Chinese families

Tang¹,

Xu²,

Zheng³

et al. 2020

Preprint

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Background: To identify the underlying genetic defect responsible for microphthalmos eyes in two three-generation Chinese families.Methods: In our study, we screened 425 potential eye disease-related genes of the proband of a three-generation Chinese family diagnosed with microphthalmos using next-generation sequencing-based target capture sequencing. Variants were filtered and analyzed to identify possible disease-causing variants before Sanger sequencing validation.Results: We enrolled two families with microphthalmos (Family 1: microphthalmos with congenital ocular coloboma and Family 2: simple microphthalmos). Two novel heterozygous mutations, PXDN c.3165C>T (p.Pro1055Pro) and PXDN c.2640C>G (p.Arg880Arg), were found in Family 1, and CRYBB2 c.481G>A (p.Gly161Arg) was found in Family 2, but none of the mutations were found in the unaffected individuals, who were phenotypically normal. Multiple orthologous sequence alignment (MSA) revealed that the CRYBB2 p.Gly161Arg mutation was a deleterious effect mutation.Conclusions: The three novel mutations found in our study extend our current understanding of the genetic basis of microphthalmos and provide early presymptomatic diagnosis and emphasize the significance of genetic diagnosis of microphthalmos.

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Section: Discussionmentioning

confidence: 99%

Three novel mutations of microphthalmos identified in two Chinese families

Tang¹,

Xu²,

Zheng³

et al. 2020

Preprint

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“…As shown in the Philly mouse model, misfolding of the mutated βB2-crystallin protein alters its aggregation properties, favoring the development of cataracts [81]. Subsequently, studies revealed additional amino acid-altering mutations in the CRYBB2 gene, in association with multiple types of congenital cataract, that result not only in structural changes in βB2-crystallin [82] but reduce also the solubility of these proteins to increase lens opacity [83][84][85][86][87][88]. Significant upregulation of βB2-crystallin occurs in several ocular pathologies, including age-related macular degeneration [89,90], glaucomatous neuropathy [91], and cauterizationinduced hypertension in rat model [91], and ocular hypertension in the rat [21,90,92].…”

Section: Ocular Pathologiesmentioning

confidence: 99%

Physiological and pathological functions of βB2-crystallins in multiple organs: a systematic review

Li¹,

Liu²,

Huang³

et al. 2021

aging

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Crystallins, the major constituent proteins of mammalian lenses, are significant not only for the maintenance of eye lens stability, transparency, and refraction, but also fulfill various physiopathological functions in extraocular tissues. βB2-crystallin, for example, is a multifunctional protein expressed in the human retina, brain, testis, ovary, and multiple tumors. Mutations in the βB2 crystallin gene or denaturation of βB2-crystallin protein are associated with cataracts, ocular pathologies, and psychiatric disorders. A prominent role for βB2crystallins in axonal growth and regeneration, as well as in dendritic outgrowth, has been demonstrated after optic nerve injury. Studies in βB2-crystallin-null mice revealed morphological and functional abnormalities in testis and ovaries, indicating βB2-crystallin contributes to male and female fertility in mice. Interestingly, although pathogenic significance remains obscure, several studies identified a clear correlation between βB2 crystallin expression and the prognosis of patients with breast cancer, colorectal cancer, prostate cancer, renal cell carcinoma, and glioblastoma in the African American population. This review summarizes the physiological and pathological functions of βB2-crystallin in the eye and other organs and tissues and discusses findings related to the expression and potential role of βB2-crystallin in tumors.

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“…Previous studies of dimeric βB2-crystallin showed concurrent dissociation of the dimer and unfolding of the N-terminal domain, and the protein could not be refolded. [369][370][371] The decreased stability is particularly surprising since it is often expected that quaternary interfaces should promote thermodynamic stability through increased enthalpic contacts and lowered entropy through studied mechanisms such as domain-swapping. [372][373][374][375] It is known that βB2-crystallin exhibits domain swapping according to the crystallized tetrameric structure, 364,372 and expected that other β-crystallins are capable of undergoing the same process.…”

Section: 32b βγ-Crystallinsmentioning

confidence: 99%

“…386,404 Heterogeneity of the crystallins helps prevent this phase-separation under physiological conditions even for proteins that operate close to their pI, like γ-crystallin, and would be expected to aggregate in solution especially under crowded conditions. 298 However, single-point mutations in crystallins can induce this phase-separation even under physiological conditions, producing light scattering aggregates and cataracts, even in the case of β-crystallins, 371,405 whose role in lens optics is not yet fully understood.…”

Section: 𝐼 = 𝐼mentioning

confidence: 99%

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Illuminating assembly dynamics regulating short-range order optics in extremely long-lived proteins

Bergman

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To those that feel they need to follow a path -you don'tLast, but most importantly, I want to thank my partner, Jenna Marie Kremer, for all her love and support over the years. She believed in myself more than I ever could and without her, none of this would have been possible. From the very first moment we met, she encouraged and supported me. After my acceptance into the PhD program at Northeastern University, she made the decision to move across the country with me -and proved how sometimes the best plans are the ones we do not make ourselves. There have been many challenges since, both expected and very unexpected, but we have faced them together. Those who have obtained a PhD undoubtedly know that it not only contains trials of intelligence, but also those of spirit. The resilience needed to finish a dissertation, both the research and the writing, is more than I would have ever predicted.Jenna has been my pillar the entire time; I survived the trials of spirit, the difficulties of research, with her to listen, comfort, challenge, and encourage, every step of the way. She makes me want to strive for the best I can, in every aspect of life, and I have accomplished more than I expected during my time as a graduate student, and it is with much thanks to her.

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A CRYBB2 mutation in a Taiwanese family with autosomal dominant cataract

Abstract: Here we identify the first Taiwanese cerulean cataract family carrying a CRYBB2_Q155X mutation.

Cited by 4 publications

References 19 publications

Three novel mutations of microphthalmos identified in two Chinese families

Three novel mutations of microphthalmos identified in two Chinese families

Physiological and pathological functions of βB2-crystallins in multiple organs: a systematic review

Illuminating assembly dynamics regulating short-range order optics in extremely long-lived proteins

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