Exome Sequencing and Epigenetic Analysis of Twins Who Are Discordant for Congenital Cataract

Purpose: To further understand genetic factors that contribute to congenital cataracts, we sought to identify early post-twinning mutational and epigenetic events that may account for the discordant phenotypes of a twin pair. Methods: A patient with a congenital cataract and her twin sister were ass...

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Bibliographic Details
Published in:Twin research and human genetics 2015-08, Vol.18 (4), p.393-398
Main Authors: Wei, Tanwei, Sun, Hui, Hu, Bo, Yang, Jie, Qiao, Chen, Yan, Ming
Format: Article
Language:English
Subjects:
Cataract - congenital
Cataract - genetics
Cataract - physiopathology
Cataracts
Child
Congenital diseases
Discordance
DNA methylation
DNA Methylation - genetics
DNA Mutational Analysis
Environmental factors
Enzymes
Epigenetics
Exome - genetics
Female
Genes
Genetic Association Studies
Genetic factors
Genomes
High-Throughput Nucleotide Sequencing
Humans
Mutation
Pedigree
Phenotypes
Point mutation
Sequence analysis
Thermal cycling
Twins
Twins, Monozygotic - genetics
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Summary:Purpose: To further understand genetic factors that contribute to congenital cataracts, we sought to identify early post-twinning mutational and epigenetic events that may account for the discordant phenotypes of a twin pair. Methods: A patient with a congenital cataract and her twin sister were assessed for genetic factors that might contribute to their discordant phenotypes by mutation screening of 11 candidate genes (CRYGC, CRYGD, CRYAA, CRYAB, CRYBA1, CRYBB1, CRYBB2, MIP, HSF4, GJA3, and GJA8), exome analysis followed by Sanger sequencing of 10 additional candidate genes (PLEKHO2, FRYL, RBP3, P2RX2, GSR, TRAM1, VEGFA, NARS2, CADPS, and TEKT4), and promoter methylation analysis of five representative genes (TRAM1, CRYAA, HSF4, VEGFA, GJA3, DCT) plus one additional candidate gene (FTL). Results: Mutation screening revealed no gene mutation differences between the patient and her twin sister for the 11 candidate genes. Exome sequencing analysis revealed variations between the twins in 442 genes, 10 of which are expressed in the eye. However, these differential variants could not be confirmed by Sanger sequencing. Furthermore, epigenetic discordance was not detected in the twin pair. Conclusions: The genomic DNA mutational and epigenetic events assessed in this study could not explain the discordance in the development of phenotypic differences between the twin pair, suggesting the possible involvement of somatic mutations or environmental factors. Identification of possible causes requires further research.
ISSN:1832-4274
1839-2628
DOI:10.1017/thg.2015.34