A novel mutation of LIM2 causes autosomal dominant membranous cataract in a Chinese family

Pei, Rui; Liang, Pengfei; Ye, Wei; Li, Ji; Ma, Jiyuan; Zhou, Jian

doi:10.18240/ijo.2020.10.02

Cited by 9 publications

(8 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mutation detection rate was 49% in the 51 families included in the study; this figure is slightly lower than reported for similar studies, which ranged from 58% to 70% [ 29 , 30 , 31 , 32 ]. The detection rate was higher than reported with Sanger sequencing [ 33 ].…”

Section: Discussioncontrasting

confidence: 62%

“…The absence of LIM2 is associated with accelerated breakdown of cytoskeletal proteins in central lens cells and cataractogenesis, as shown in LIM2 -deficient mice models designed by Shi et al and Steele et al [ 26 , 28 ]. Missense mutations have been associated with autosomal recessive cataracts (c.313T>G (p.Phe105Val); c.587G>A (p.Gly154Glu); c.233G>A (p.Gly78Asp)) [ 27 ], and one missense heterozygous mutation causing membranous, lamellar and nuclear cataract (c.388C>T) has recently been reported in European and Asian populations [ 29 , 30 ]. In our cohort, we identified two families presenting with this variant.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular and Genetic Mechanism of Non-Syndromic Congenital Cataracts. Mutation Screening in Spanish Families

Fernández-Alcalde

Nieves-Moreno

Noval

et al. 2021

Genes

View full text Add to dashboard Cite

Our purpose was to identify mutations responsible for non-syndromic congenital cataracts through the implementation of next-generation sequencing (NGS) in our center. A sample of peripheral blood was obtained from probands and willing family members and genomic DNA was extracted from leukocytes. DNA was analyzed implementing a panel (OFTv2.1) including 39 known congenital cataracts disease genes. 62 probands from 51 families were recruited. Pathogenic or likely pathogenic variants were identified in 32 patients and 25 families; in 16 families (64%) these were de novo mutations. The mutation detection rate was 49%. Almost all reported mutations were autosomal dominant. Mutations in crystallin genes were found in 30% of the probands. Mutations in membrane proteins were detected in seven families (two in GJA3 and five in GJA8). Mutations in LIM2 and MIP were each found in three families. Other mutations detected affected EPHA2, PAX6, HSF4 and PITX3. Variants classified as of unknown significance were found in 5 families (9.8%), affecting CRYBB3, LIM2, EPHA2, ABCB6 and TDRD7. Mutations lead to different cataract phenotypes within the same family.

show abstract

Section: Discussioncontrasting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Molecular and Genetic Mechanism of Non-Syndromic Congenital Cataracts. Mutation Screening in Spanish Families

Fernández-Alcalde

Nieves-Moreno

Noval

et al. 2021

Genes

View full text Add to dashboard Cite

show abstract

“…are closely associated with cataract ( Li et al, 2020 ), and autosomal dominant congenital cataract is the most common mode of inheritance ( Berry et al, 2020a ). To date, the occurrence of congenital cataract has been linked with genetic variants in at least 50 genes involved in lens structure and development ( Berry et al, 2020b ; Shiels and Hejtmancik, 2017 ), including crystallin genes ( CRYAA , CRYAB , CRYBB1 , CRYBB2 , CRYBB3 , CRYBA1/A3 , CRYBA2 , CRYBA4 , CRYGC , CRYGD, and CRYGS ) ( Bhat, 2003 ; Zhuang et al, 2019 ), membrane protein genes ( GJA3 , GJA8 , MIP, and LIM2 ) ( Berry et al, 2000 ; Beyer et al, 2013 ; Pei et al, 2020 ), growth and transcription factor genes ( PITX3 , MAF, and HSF4 ) ( Anand et al, 2018 ), beaded filament structural protein genes ( BFSP1 and BFSP2 ) ( Song et al, 2009 ), and other genes ( CHMP4B and EPHA2 ) ( Dave et al, 2016 ; Shiels et al, 2007 ). Although these findings have made tremendous contributions to our understanding of the genetic etiology of congenital cataract, new causative genes as well as the underlying molecular mechanisms remain to be discovered ( Berry et al, 2020a ).…”

Section: Introductionmentioning

confidence: 99%

Disruption of PIKFYVE causes congenital cataract in human and zebrafish

Mei¹,

Wang

et al. 2022

eLife

View full text Add to dashboard Cite

Congenital cataract, an ocular disease predominantly occurring within the first decade of life, is one of the leading causes of blindness in children. However, the molecular mechanisms underlying the pathogenesis of congenital cataract remain incompletely defined. Through whole-exome sequencing of a Chinese family with congenital cataract, we identified a potential pathological variant (p.G1943E) in PIKFYVE, which is located in the PIP kinase domain of the PIKFYVE protein. We demonstrated that heterozygous/homozygous disruption of PIKFYVE kinase domain, instead of overexpression of PIKFYVEG1943E in zebrafish mimicked the cataract defect in human patients, suggesting that haploinsufficiency, rather than dominant-negative inhibition of PIKFYVE activity caused the disease. Phenotypical analysis of pikfyve zebrafish mutants revealed that loss of Pikfyve caused aberrant vacuolation (accumulation of Rab7+Lc3+ amphisomes) in lens cells, which was significantly alleviated by treatment with the V-ATPase inhibitor bafilomycin A1 (Baf-A1). Collectively, we identified PIKFYVE as a novel causative gene for congenital cataract and pinpointed the potential application of Baf-A1 for the treatment of congenital cataract caused by PIKFYVE deficiency.

show abstract

“…Li, Chen, Yan, & Yao, 2020), and autosomal dominant congenital cataract is the most common mode of inheritance (Berry, Georgiou, et al, 2020). To date, mutations in at least 50 genes involved in lens structure and development have been linked to isolated congenital cataract (Berry, Ionides, et al, 2020;Shiels & Hejtmancik, 2017), including crystallin genes (CRYAA, CRYAB, CRYBB1, CRYBB2, CRYBB3, CRYBA1/A3, CRYBA2, CRYBA4, CRYGC, CRYGD and CRYGS) (Bhat, 2003;Zhuang et al, 2019), membrane protein genes (GJA3, GJA8, MIP and LIM2) (Berry, Francis, Kaushal, Moore, & Bhattacharya, 2000;Beyer, Ebihara, & Berthoud, 2013;Pei et al, 2020), growth and transcription factor genes (PITX3, MAF and HSF4) (Anand, Agrawal, Slavotinek, & Lachke, 2018), beaded filament structural protein genes (BFSP1 and BFSP2) (Song et al, 2009) and other genes (CHMP4B and EPHA2) (Dave et al, 2016;Shiels et al, 2007). Although these findings have made tremendous contributions to our understanding of the genetic etiology of congenital cataract, new disease causative genes as well as the underlying molecular mechanisms remain to be discovered (Berry, Georgiou, et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Mutations in PIKFYVE cause autosomal dominant congenital cataract

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

Congenital cataract, an ocular disease predominantly occurring within the first decade of life, is one of the leading causes of blindness in children. Through whole exome sequencing of a Chinese family with congenital cataract, we identified a disease-causing mutation (p.G1943E) in PIKFYVE, which affecting the PIP kinase domain of the PIKfyve protein. We demonstrated that heterozygous/homozygous disruption of PIKfyve kinase domain, instead of overexpression of PIKFYVEG1943E in zebrafish mimicked the cataract defect in human patients, suggesting that haploinsufficiency, rather than dominant-negative inhibition of PIKfyve activity caused the disease. Phenotypical analysis of pikfyve zebrafish mutants revealed that loss of Pikfyve caused aberrant vacuolation (accumulation of Rab7+Lc3+ amphisomes) in lens cells, which was significantly alleviated by treatment with the V-ATPase inhibitor bafilomycin A1 (Baf-A1). Collectively, we identified PIKFYVE as a novel causative gene for congenital cataract and demonstrated the potential application of Baf-A1 in treatment of congenital cataract.

show abstract

A novel mutation of LIM2 causes autosomal dominant membranous cataract in a Chinese family

Cited by 9 publications

References 22 publications

Molecular and Genetic Mechanism of Non-Syndromic Congenital Cataracts. Mutation Screening in Spanish Families

Molecular and Genetic Mechanism of Non-Syndromic Congenital Cataracts. Mutation Screening in Spanish Families

Disruption of PIKFYVE causes congenital cataract in human and zebrafish

Mutations in PIKFYVE cause autosomal dominant congenital cataract

Contact Info

Product

Resources

About