Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract

Rechsteiner, Delia; Issler, Lydia S.; Koller, Samuel; Lang, Elena; Bähr, Luzy; Feil, Silke; Rüegger, Christoph M.; Kottke, Raimund; Toelle, Sandra P.; Zweifel, Noemi; Steindl, Katharina; Joset, Pascal; Zweier, Christiane; Suter, Aude-Annick; Gogoll, Laura; Haas, Cordula; Berger, Wolfgang; Gerth‐Kahlert, Christina

doi:10.1001/jamaophthalmol.2021.0385

Cited by 21 publications

(23 citation statements)

References 67 publications

(101 reference statements)

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“…To date, a total of 32 variants in CRYGC gene have been reported to be associated with congenital cataract ( Heon et al, 1999 ; Ren et al, 2000 ; Santhiya et al, 2002 ; Gonzalez-Huerta et al, 2007 ; Devi et al, 2008 ; Yao et al, 2008 ; Zhang et al, 2009 ; Kumar et al, 2011 ; Guo et al, 2012 ; Li et al, 2012 ; Kondo et al, 2013 ; Reis et al, 2013 ; Gillespie et al, 2014 ; Prokudin et al, 2014 ; Li et al, 2016 ; Ma et al, 2016 ; Patel et al, 2017 ; Sun et al, 2017 ; Zhong et al, 2017 ; Astiazaran et al, 2018 ; Li et al, 2018 ; Zhang et al, 2019 ; Zhuang et al, 2019 ; Berry et al, 2020 ; Taylan Sekeroglu et al, 2020 ; Fernandez-Alcalde et al, 2021 ; Karahan et al, 2021 ; Rechsteiner et al, 2021 ), but there were few reports about the de novo mutations. In 2017, Zhong et al reported a frameshift mutation (p.Asp65ThrfsX38) which might be de novo ( Zhong et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…In 2017, Zhong et al reported a frameshift mutation (p.Asp65ThrfsX38) which might be de novo ( Zhong et al, 2017 ). In 2021, Rechsteiner et al reported a de novo mutation p.Glu107GlyfsX56, which causes cataracts and microphthalmia ( Rechsteiner et al, 2021 ), and Fernández-Alcalde et al reported a de novo mutation p.Leu145GlyfsX5 ( Fernandez-Alcalde et al, 2021 ). In the present study, a de novo frameshift variant (c.394delG, p.V132Sfs*15) was identified in CRYGC gene as the cause of a patient with congenital cataract and microphthalmia.…”

Section: Discussionmentioning

confidence: 99%

“…There 15 variants were reported to cause cataracts and additional ocular signs among all the 32 reported CRYGC variants. Microcornea was the most common additional ocular sign ( Zhang et al, 2009 ; Guo et al, 2012 ; Reis et al, 2013 ; Patel et al, 2017 ; Sun et al, 2017 ; Zhong et al, 2017 ; Rechsteiner et al, 2021 ). The phenotypic heterogeneity could be due to unidentified modifier genes ( Astiazaran et al, 2018 ) or some unknown mechanisms in which CRYGC takes part during eye development.…”

Section: Discussionmentioning

confidence: 99%

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Case Report: A de novo Variant of CRYGC Gene Associated With Congenital Cataract and Microphthalmia

Zheng

Deng

et al. 2022

Front. Genet.

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Background: Congenital cataract is one of the most common causes of blindness in children. A rapid and accurate genetic diagnosis benefit the patients in the pediatric department. The current study aims to identify the genetic defects in a congenital cataract patient without a family history.Case presentation: A congenital cataract patient with microphthalmia and nystagmus was recruited for this study. Trio-based whole-exome sequencing revealed a de novo variant (c.394delG, p.V132Sfs*15) in CRYGC gene. According to the American College of Medical Genetics and Genomics (ACMG) criteria, the variant could be annontated as pathogenic.Conclusion: Our findings provide new knowledge of the variant spectrum of CRYGC gene and are essential for understanding the heterogeneity of cataracts in the Chinese population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Case Report: A de novo Variant of CRYGC Gene Associated With Congenital Cataract and Microphthalmia

Zheng

Deng

et al. 2022

Front. Genet.

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“…Next-Generation Sequencing (NGS), also known as high-throughput sequencing, has been increasingly applied to congenital cataract [ 4 , 8 ]. To date, genetic studies have identified mutations from more than 87 causative genes in non-systemic congenital cataract, and genetic mutations remain the leading cause of congenital cataracts (data from Cat-Map http://cat-map.wustl.edu/ ) [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Novel SOX2 mutation in autosomal dominant cataract-microcornea syndrome

Lin

et al. 2022

BMC Ophthalmol

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Background Congenital cataract-microcornea syndrome (CCMC) is characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Although several causative genes have been reported in patients with CCMC, the genetic etiology of CCMC is yet to be clearly understood. Purpose To unravel the genetic cause of autosomal dominant family with CCMC. Methods All patients and available family members underwent a comprehensive ophthalmologic clinical examination in the hospital by expert ophthalmologists and carried out to clinically diagnosis. All the patients were screened by whole-exome sequencing and then validated using co-segregation by Sanger sequencing. Results Four CCMC patients from a Chinese family and five unaffected family members were enrolled in this study. Using whole-exome sequencing, a missense mutation c.295G > T (p.A99S, NM_003106.4) in the SOX2 gene was identified and validated by segregation analysis. In addition, this missense mutation was predicted to be damaging by multiple predictive tools. Variant p.Ala99Ser was located in a conservation high mobility group (HMG)-box domain in SOX2 protein, with a potential pathogenic impact of p.Ala99Ser on protein level. Conclusions A novel missense mutation (c.295G > T, p.Ala99Ser) in the SOX2 gene was found in this Han Chinese family with congenital cataract and microcornea. Our study determined that mutations in SOX2 were associated with CCMC, warranting further investigations on the pathogenesis of this disorder. This result expands the mutation spectrum of SOX2 and provides useful information to study the molecular pathogenesis of CCMC.

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“…At present, 29 variants in the human MIP gene associated with CCs have been identified, and most of the variants are located in the H4, H5, H6, C-TIDs, and loop C of the MIP [ 6 ]. The NP_036196.1:p.R33C variant located in the extracellular loop A and the clinical phenotypes caused by this variant previously reported in different families with CCs included total cataract and nuclear cataract with posterior polar opacity [ 7 , 8 , 9 , 10 , 11 ]. Herein, we found a novel cataract phenotype, anterior umbilication of the lens, and nuclear or total cataract in a Han Chinese family with CCs caused by the p.R33C variant in the MIP gene.…”

Section: Introductionmentioning

confidence: 99%

Anterior Umbilication of Lens in a Family with Congenital Cataracts Associated with a Missense Mutation of MIP Gene

Cheng

Wang²,

Wang³

et al. 2022

Genes

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Congenital cataracts (CCs) have significant genotypic and phenotypic heterogeneity. The major intrinsic protein (MIP) gene, one of the causative genes of CCs, plays a vital role in maintaining the homeostasis and transparency of the lens. In this study, we identified a unique phenotype of anterior umbilication of the lens in a four-generation pedigree with CCs. All patients in the observed family had nystagmus, nuclear cataracts, and elongated axial lengths compared with their healthy counterparts except for patient I:2, whose axial length was unavailable, and patientII:4, who had total cataracts. We confirmed, using Sanger sequencing based on whole-exon sequencing (WES) data, that all patients carried a heterozygous variant NM_012064.4:c.97C > T (NP_036196.1:p.R33C) in their MIP gene. To our knowledge, 29 variants of the human MIP gene and the relative phenotypes associated with CCs have been identified. Nevertheless, this is the first report on the anterior umbilication of the lens with nuclear or total opacity caused by the c.97C > T (p.R33C) variant in the MIP gene. These results also provide evidence that the elongated axial length might be associated with this variant. This study further confirms the phenotypic heterogeneity of CCs.

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Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract

Cited by 21 publications

References 67 publications

Case Report: A de novo Variant of CRYGC Gene Associated With Congenital Cataract and Microphthalmia

Case Report: A de novo Variant of CRYGC Gene Associated With Congenital Cataract and Microphthalmia

Novel SOX2 mutation in autosomal dominant cataract-microcornea syndrome

Anterior Umbilication of Lens in a Family with Congenital Cataracts Associated with a Missense Mutation of MIP Gene

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