Molecular Genetic Analysis of Ukrainian Families with Congenital Cataracts
This study was designed to identify the pathogenic variants in five Ukrainian families with autosomal dominant congenital cataracts. Cataracts can be defined broadly as any opacity of the crystalline lens. Lens development is orchestrated by transcription factors. Disease-causing variants in transcr...
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MDPI AG
2022-12-01
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| author | Xiaodong Jiao Mariia Viswanathan Nadiia Fedorivna Bobrova Tatiana Viktorivna Romanova J. Fielding Hejtmancik |
| author_facet | Xiaodong Jiao Mariia Viswanathan Nadiia Fedorivna Bobrova Tatiana Viktorivna Romanova J. Fielding Hejtmancik |
| author_sort | Xiaodong Jiao |
| collection | DOAJ |
| description | This study was designed to identify the pathogenic variants in five Ukrainian families with autosomal dominant congenital cataracts. Cataracts can be defined broadly as any opacity of the crystalline lens. Lens development is orchestrated by transcription factors. Disease-causing variants in transcription factors and their developmental target genes, including the lens crystallins, are associated with congenital cataracts and other eye diseases. Whole-exome sequencing identified heterozygous disease-causing variants in five Ukrainian families with autosomal dominant congenital cataracts and cosegregation with cataracts was confirmed using Sanger sequencing. Family 97001 showed a missense variant (c.341T>A: p.L114Q) in HSF4; family 97003 showed a missense variant (c.53A>T: p.N18I) in CRYGA; family 97004 showed a missense variant (c. 82G>A: p.V28M) in GJA3; family 97006 showed a missense variant (c.83C>T: p. P28L) in CRYGC; and family 97008 showed a single-base insertion resulting in a frameshift (c.443_444insA: p. Met148IfsTer51) in PAX6. All five families are associated with congenital cataracts. Overall, we report four novel mutations in HSF4, CRYGA, CRYGC and PAX6, and one previously reported mutation in GJA3 that cause autosomal dominant congenital cataracts. |
| first_indexed | 2024-03-09T13:09:44Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2227-9067 |
| language | English |
| last_indexed | 2024-03-09T13:09:44Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Children |
| spelling | doaj.art-8bf6278dcf844119b97d288483c7269b2023-11-30T21:43:03ZengMDPI AGChildren2227-90672022-12-011015110.3390/children10010051Molecular Genetic Analysis of Ukrainian Families with Congenital CataractsXiaodong Jiao0Mariia Viswanathan1Nadiia Fedorivna Bobrova2Tatiana Viktorivna Romanova3J. Fielding Hejtmancik4Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USAVision Care Readiness Section, Vision Center of Excellence, Defense Health Agency Research and Engineering, Bethesda, MD 20889, USADepartment of Pediatric Ophthalmic Pathology, State Institution “The Filatov Institute of Eye Diseases and Tissue Therapy of The National Academy of Medical Sciences of Odessa, Ukraine”, 65000 Odessa, UkraineDepartment of Pediatric Ophthalmic Pathology, State Institution “The Filatov Institute of Eye Diseases and Tissue Therapy of The National Academy of Medical Sciences of Odessa, Ukraine”, 65000 Odessa, UkraineOphthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USAThis study was designed to identify the pathogenic variants in five Ukrainian families with autosomal dominant congenital cataracts. Cataracts can be defined broadly as any opacity of the crystalline lens. Lens development is orchestrated by transcription factors. Disease-causing variants in transcription factors and their developmental target genes, including the lens crystallins, are associated with congenital cataracts and other eye diseases. Whole-exome sequencing identified heterozygous disease-causing variants in five Ukrainian families with autosomal dominant congenital cataracts and cosegregation with cataracts was confirmed using Sanger sequencing. Family 97001 showed a missense variant (c.341T>A: p.L114Q) in HSF4; family 97003 showed a missense variant (c.53A>T: p.N18I) in CRYGA; family 97004 showed a missense variant (c. 82G>A: p.V28M) in GJA3; family 97006 showed a missense variant (c.83C>T: p. P28L) in CRYGC; and family 97008 showed a single-base insertion resulting in a frameshift (c.443_444insA: p. Met148IfsTer51) in PAX6. All five families are associated with congenital cataracts. Overall, we report four novel mutations in HSF4, CRYGA, CRYGC and PAX6, and one previously reported mutation in GJA3 that cause autosomal dominant congenital cataracts.https://www.mdpi.com/2227-9067/10/1/51lensautosomal dominant congenital cataractwhole-exome sequencing |
| spellingShingle | Xiaodong Jiao Mariia Viswanathan Nadiia Fedorivna Bobrova Tatiana Viktorivna Romanova J. Fielding Hejtmancik Molecular Genetic Analysis of Ukrainian Families with Congenital Cataracts Children lens autosomal dominant congenital cataract whole-exome sequencing |
| title | Molecular Genetic Analysis of Ukrainian Families with Congenital Cataracts |
| title_full | Molecular Genetic Analysis of Ukrainian Families with Congenital Cataracts |
| title_fullStr | Molecular Genetic Analysis of Ukrainian Families with Congenital Cataracts |
| title_full_unstemmed | Molecular Genetic Analysis of Ukrainian Families with Congenital Cataracts |
| title_short | Molecular Genetic Analysis of Ukrainian Families with Congenital Cataracts |
| title_sort | molecular genetic analysis of ukrainian families with congenital cataracts |
| topic | lens autosomal dominant congenital cataract whole-exome sequencing |
| url | https://www.mdpi.com/2227-9067/10/1/51 |
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