Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family

Li, Bin; Lü, Bin; Guo, Xingming; Hu, Shenghui; Zhao, Guizhe; Huang, Weihong; Hu, Jianzhong; Song, Kun

doi:10.1155/2020/7054315

Cited by 6 publications

(5 citation statements)

References 54 publications

(73 reference statements)

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“…Wolframin variants are reported to result in ER stress and loss of ER function, disrupting the export of vesicle cargo proteins such as insulin. 17 To date four autosomal dominant families (including one in this study) and three sporadic cases have been documented with variants in WFS1 causing isolated cataracts or other WS pathologies [18][19][20][21] (table 3). The majority of recessive WFS1 inactivating variants cause typical WS, whereas dominant non-inactivating variants are associated with less severe, but more varied, phenotypes.…”

Section: Discussionmentioning

confidence: 87%

Multimorbidity due to novel pathogenic variants in theWFS1/RP1/NOD2genes: autosomal dominant congenital lamellar cataract, retinitis pigmentosa and Crohn’s disease in a British family

et al. 2023

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BackgroundA five generation family has been analysed by whole exome sequencing (WES) for genetic associations with the multimorbidities of congenital cataract (CC), retinitis pigmentosa (RP) and Crohn’s disease (CD).MethodsWES was performed for unaffected and affected individuals within the family pedigree followed by bioinformatic analyses of these data to identify disease-causing variants with damaging pathogenicity scores.ResultsA novel pathogenic missense variant inWFS1: c.1897G>C; p.V633L, a novel pathogenic nonsense variant inRP1: c.6344T>G; p.L2115* and a predicted pathogenic missense variant inNOD2: c.2104C>T; p.R702W are reported. The three variants cosegregated with the phenotypic combinations of autosomal dominant CC, RP and CD within individual family members.ConclusionsHere, we report multimorbidity in a family pedigree listed on a CC register, which broadens the spectrum of potential cataract associated genes to include bothRP1andNOD2.

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Section: Discussionmentioning

confidence: 87%

Multimorbidity due to novel pathogenic variants in theWFS1/RP1/NOD2genes: autosomal dominant congenital lamellar cataract, retinitis pigmentosa and Crohn’s disease in a British family

et al. 2023

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“…Boatz et al found that P24T variants aggregated under in vivo conditions with a native-like fold by a non-amyloid mechanism, which was considered to be the surfacemediated changes in protein-protein interactions [39]. Li et al revealed that P24T mutant changed a pyrrole ring of the wild type into a hydrophilic structure, affecting the correct folding of the protein [35].…”

Section: Discussionmentioning

confidence: 99%

Congenital coralliform cataract is the predominant consequence of a recurrent mutation in the CRYGD gene

Wang

et al. 2023

Preprint

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Background: Congenital cataract is a leading cause of treatable childhood blindness and both clinically and genetically heterogeneous. Among the already characterized phenotypes, coralliform cataract is a rare special form of congenital cataracts. Although previous studies had shown that mutations in the γD-crystallin (CRYGD) gene can result in congenital coralliform cataracts, no conclusive genotype-phenotype correlation might be drawn. Here we aimed to identify the spectrum and frequency of CRYGD gene mutations in congenital coralliform cataracts of Chinese origin. Methods: The medical records of 392 Chinese families with congenital cataracts were reviewed between January 2011 and December 2021. The families, clinically documented to have congenital coralliform cataracts, were screened for mutations in candidate CRYGD gene. The genomic DNA of all subjects was extracted from peripheral blood leukocytes. PCR amplified and direct sequencing were performed to identify the disease-causing mutation. Results: A total of 12 families with coralliform cataracts were recruited in this study in the past 10 years, accounting for 3.1% of the families with congenital cataracts. Of the 12 families, all affected individuals presented with bilateral non-progressive coralliform cataracts since birth. A recurrent c.70 C>A (p. P24T) mutation in CRYGD was identified in 10 families (83.3%) with congenital cataract, which co-segregated with all affected individuals and was not observed in unaffected family members or ethnically matched normal controls. Conclusions: The coralliform cataract is characterized by being bilateral, non-progressive and present at birth. A recurrent P24T CRYGD mutation occurs independently in 83.3% of the Chinese families with congenital coralliform cataracts and most likely represents a mutational hot spot, which underscore the relations between coralliform cataract and P24T CRYGD.

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“…Boatz et al found that p.P24T variant aggregated under in vivo conditions with a native-like fold by a non-amyloid mechanism, which was considered to be the surface-mediated changes in protein–protein interactions [ 18 ]. Li et al revealed that p.P24T mutant changed a pyrrole ring of the wild type into a hydrophilic structure, affecting the correct folding of the protein [ 19 ]. The findings presumed that the p.P24T might initiate aggregation or polymerization and result in the formation of CC.…”

Section: Discussionmentioning

confidence: 99%

“…p.P24T was also found to be responsible for several different phenotypes of CC except for coralliform cataract, e.g., lamellar cataract, cerulean cataract, the fasciculi form cataract and total cataract [ 9 – 14 , 19 , 24 , 26 – 39 ]. Although there was variability in cataract phenotypes among the p.P24T-bearing families, coralliform cataract was the most common phenotype, and more importantly, all Chinese families including our ten families were involved coralliform cataract.…”

Section: Discussionmentioning

confidence: 99%

Congenital coralliform cataract is the predominant consequence of a recurrent mutation in the CRYGD gene

Wang

et al. 2023

Orphanet J Rare Dis

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Background Congenital cataract is a leading cause of treatable childhood blindness and both clinically and genetically heterogeneous. Among the already characterized phenotypes, coralliform cataract is a rare special form of congenital cataracts. Although previous studies had shown that mutations in the γD-crystallin (CRYGD) can result in congenital coralliform cataracts, no conclusive genotype-phenotype correlation might be drawn. Here we aimed to identify the spectrum and frequency of CRYGD gene mutations in congenital coralliform cataracts of Chinese origin. Methods The medical records of 392 Chinese families with congenital cataracts were reviewed between January 2011 and December 2021. The families, clinically documented to have congenital coralliform cataracts, were screened for mutations in candidate CRYGD gene. The genomic DNA of all subjects was extracted from peripheral blood leukocytes. PCR amplified and direct sequencing were performed to identify the disease-causing mutation. Results A total of 12 families with coralliform cataracts were recruited in this study in the past 10 years, accounting for 3.1% of the families with congenital cataracts. Of the 12 families, all affected individuals presented with bilateral non-progressive coralliform cataracts since birth, with the best-corrected Snellen visual acuities ranging from 20/200 to 20/25. A recurrent c.70 C > A (p. P24T) mutation in CRYGD was identified in 10 families (83.3%) with congenital cataract, which co-segregated with all affected individuals and was not observed in unaffected family members or ethnically matched normal controls. Conclusions The coralliform cataract is characterized by being bilateral, non-progressive and present at birth. A recurrent p.P24T CRYGD mutation occurs independently in 83.3% of the Chinese families with congenital coralliform cataracts and most likely represents a mutational hot spot, which underscore the relations between coralliform cataract and p.P24T CRYGD.

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Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family

Cited by 6 publications

References 54 publications

Multimorbidity due to novel pathogenic variants in theWFS1/RP1/NOD2genes: autosomal dominant congenital lamellar cataract, retinitis pigmentosa and Crohn’s disease in a British family

Multimorbidity due to novel pathogenic variants in theWFS1/RP1/NOD2genes: autosomal dominant congenital lamellar cataract, retinitis pigmentosa and Crohn’s disease in a British family

Congenital coralliform cataract is the predominant consequence of a recurrent mutation in the CRYGD gene

Congenital coralliform cataract is the predominant consequence of a recurrent mutation in the CRYGD gene

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