A novel mutation of LIM2 causes autosomal dominant membranous cataract in a Chinese family
AIM: To identify mutations in the genes of a four-generation Chinese family with congenital membranous cataracts and investigate the morphologic changes and possible functional damage underlying the role of the mutant gene. METHODS: Whole exome analysis of thirteen members of a four-generation pedi...
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doaj-0e09716680db409cbb1664aa40f107d12020-11-25T01:22:18ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982020-10-0113101512152010.18240/ijo.2020.10.02A novel mutation of LIM2 causes autosomal dominant membranous cataract in a Chinese familyRui Pei0Peng-Fei Liang1Wei Ye2Ji Li3Ji-Yuan Ma4Jian Zhou5Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, ChinaDepartment of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, ChinaDepartment of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, ChinaDepartment of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, ChinaDepartment of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, ChinaDepartment of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, ChinaAIM: To identify mutations in the genes of a four-generation Chinese family with congenital membranous cataracts and investigate the morphologic changes and possible functional damage underlying the role of the mutant gene. METHODS: Whole exome analysis of thirteen members of a four-generation pedigree affected with congenital membranous cataracts was performed; co-segregation analysis of identified variants was validated by Sanger sequencing. All members underwent detailed physical and complete eye examinations. The physical changes caused by the mutation were analyzed in silico through homology modeling. The lens fiber block from a patient was observed under a scanning electron microscope (SEM). Cell membrane proteins and cytoplasmic proteins from the human lenses donated by one patient with cataract in this family and from the dislocated lens resulted from the penetrating ocular trauma of a patient unrelated with this family were extracted, and the expression and localization of MP20 and Cx46 were detected by Western blot (WB) assay in these proteins. RESULTS: A novel LIM2 heterozygous mutation (c.388C>T, p.R130C) was identified with congenital membranous cataracts inherited by an autosomal dominant (AD) pattern. Nystagmus and amblyopia were observed in all patients of this family, and exotropia and long axial length were observed in most patients. A/B ultrasound scan and ultrasound biomicroscopy revealed obvious thin crystalline lenses from 1.7 to 2.7 mm in central thickness in all cataract eyes. The bioinformatic analysis showed that the mutation was deleterious to the physiological function of LIM2-encoded MP20. Furthermore, by SEM, ultrastructure of the cataract nucleus showed that lens fiber cells (LFCs) remained morphologic characteristics of immature fiber cells, including flap cell surface with straight edges and lacking normal ball-and-socket joint boundaries, which implied that the differentiation of LFCs might be inhibited. Accumulation of MP20 and Cx46 in the cytoplasm was observed in the cytoplasm of the LFCs in human cataract lens. CONCLUSION: We identify a novel heterozygous LIM2 (c.388C>T, p.R130C) mutation inherited by an AD pattern. This LIM2 mutation causes the abnormal sub-localization of MP20 and Cx46 in LFCs resulting in membranous cataracts.http://www.ijo.cn/en_publish/2020/10/20201002.pdflim2mp20congenital cataractmissense mutationdifferentiation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rui Pei Peng-Fei Liang Wei Ye Ji Li Ji-Yuan Ma Jian Zhou |
spellingShingle |
Rui Pei Peng-Fei Liang Wei Ye Ji Li Ji-Yuan Ma Jian Zhou A novel mutation of LIM2 causes autosomal dominant membranous cataract in a Chinese family International Journal of Ophthalmology lim2 mp20 congenital cataract missense mutation differentiation |
author_facet |
Rui Pei Peng-Fei Liang Wei Ye Ji Li Ji-Yuan Ma Jian Zhou |
author_sort |
Rui Pei |
title |
A novel mutation of LIM2 causes autosomal dominant membranous cataract in a Chinese family |
title_short |
A novel mutation of LIM2 causes autosomal dominant membranous cataract in a Chinese family |
title_full |
A novel mutation of LIM2 causes autosomal dominant membranous cataract in a Chinese family |
title_fullStr |
A novel mutation of LIM2 causes autosomal dominant membranous cataract in a Chinese family |
title_full_unstemmed |
A novel mutation of LIM2 causes autosomal dominant membranous cataract in a Chinese family |
title_sort |
novel mutation of lim2 causes autosomal dominant membranous cataract in a chinese family |
publisher |
Press of International Journal of Ophthalmology (IJO PRESS) |
series |
International Journal of Ophthalmology |
issn |
2222-3959 2227-4898 |
publishDate |
2020-10-01 |
description |
AIM: To identify mutations in the genes of a four-generation Chinese family with congenital membranous cataracts and investigate the morphologic changes and possible functional damage underlying the role of the mutant gene.
METHODS: Whole exome analysis of thirteen members of a four-generation pedigree affected with congenital membranous cataracts was performed; co-segregation analysis of identified variants was validated by Sanger sequencing. All members underwent detailed physical and complete eye examinations. The physical changes caused by the mutation were analyzed in silico through homology modeling. The lens fiber block from a patient was observed under a scanning electron microscope (SEM). Cell membrane proteins and cytoplasmic proteins from the human lenses donated by one patient with cataract in this family and from the dislocated lens resulted from the penetrating ocular trauma of a patient unrelated with this family were extracted, and the expression and localization of MP20 and Cx46 were detected by Western blot (WB) assay in these proteins.
RESULTS: A novel LIM2 heterozygous mutation (c.388C>T, p.R130C) was identified with congenital membranous cataracts inherited by an autosomal dominant (AD) pattern. Nystagmus and amblyopia were observed in all patients of this family, and exotropia and long axial length were observed in most patients. A/B ultrasound scan and ultrasound biomicroscopy revealed obvious thin crystalline lenses from 1.7 to 2.7 mm in central thickness in all cataract eyes. The bioinformatic analysis showed that the mutation was deleterious to the physiological function of LIM2-encoded MP20. Furthermore, by SEM, ultrastructure of the cataract nucleus showed that lens fiber cells (LFCs) remained morphologic characteristics of immature fiber cells, including flap cell surface with straight edges and lacking normal ball-and-socket joint boundaries, which implied that the differentiation of LFCs might be inhibited. Accumulation of MP20 and Cx46 in the cytoplasm was observed in the cytoplasm of the LFCs in human cataract lens.
CONCLUSION: We identify a novel heterozygous LIM2 (c.388C>T, p.R130C) mutation inherited by an AD pattern. This LIM2 mutation causes the abnormal sub-localization of MP20 and Cx46 in LFCs resulting in membranous cataracts. |
topic |
lim2 mp20 congenital cataract missense mutation differentiation |
url |
http://www.ijo.cn/en_publish/2020/10/20201002.pdf |
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