Non-Syndromic Dentinogenesis Imperfecta Caused by Mild Mutations in <i>COL1A2</i>
Hereditary dentin defects can be categorized as a syndromic form predominantly related to osteogenesis imperfecta (OI) or isolated forms without other non-oral phenotypes. Mutations in the gene encoding dentin sialophosphoprotein (DSPP) have been identified to cause dentinogenesis imperfecta (DGI) T...
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MDPI AG
2021-06-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/11/6/526 |
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| author | Yejin Lee Youn Jung Kim Hong-Keun Hyun Jae-Cheoun Lee Zang Hee Lee Jung-Wook Kim |
| author_facet | Yejin Lee Youn Jung Kim Hong-Keun Hyun Jae-Cheoun Lee Zang Hee Lee Jung-Wook Kim |
| author_sort | Yejin Lee |
| collection | DOAJ |
| description | Hereditary dentin defects can be categorized as a syndromic form predominantly related to osteogenesis imperfecta (OI) or isolated forms without other non-oral phenotypes. Mutations in the gene encoding dentin sialophosphoprotein (DSPP) have been identified to cause dentinogenesis imperfecta (DGI) Types II and III and dentin dysplasia (DD) Type II. While DGI Type I is an OI-related syndromic phenotype caused mostly by monoallelic mutations in the genes encoding collagen type I alpha 1 chain (<i>COL1A1</i>) and collagen type I alpha 2 chain (<i>COL1A2</i>). In this study, we recruited families with non-syndromic dentin defects and performed candidate gene sequencing for <i>DSPP</i> exons and exon/intron boundaries. Three unrelated Korean families were further analyzed by whole-exome sequencing due to the lack of the <i>DSPP</i> mutation, and heterozygous <i>COL1A2</i> mutations were identified: c.3233G>A, p.(Gly1078Asp) in Family 1 and c.1171G>A, p.(Gly391Ser) in Family 2 and 3. Haplotype analysis revealed different disease alleles in Families 2 and 3, suggesting a mutational hotspot. We suggest expanding the molecular genetic etiology to include <i>COL1A2</i> for isolated dentin defects in addition to <i>DSPP</i>. |
| first_indexed | 2024-03-10T10:36:00Z |
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| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T10:36:00Z |
| publishDate | 2021-06-01 |
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| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-42457e7afebb49c0948a8ddf3cb894652023-11-21T23:19:39ZengMDPI AGJournal of Personalized Medicine2075-44262021-06-0111652610.3390/jpm11060526Non-Syndromic Dentinogenesis Imperfecta Caused by Mild Mutations in <i>COL1A2</i>Yejin Lee0Youn Jung Kim1Hong-Keun Hyun2Jae-Cheoun Lee3Zang Hee Lee4Jung-Wook Kim5Department of Pediatric Dentistry, School of Dentistry & DRI, Seoul National University, Seoul 03080, KoreaDepartment of Molecular Genetics, School of Dentistry & DRI, Seoul National University, Seoul 03080, KoreaDepartment of Pediatric Dentistry, School of Dentistry & DRI, Seoul National University, Seoul 03080, KoreaSeoul Chungdam Children’s Dental Center, Seoul 06072, KoreaDepartment of Cell and Developmental Biology, School of Dentistry & DRI, Seoul National University, Seoul 03080, KoreaDepartment of Pediatric Dentistry, School of Dentistry & DRI, Seoul National University, Seoul 03080, KoreaHereditary dentin defects can be categorized as a syndromic form predominantly related to osteogenesis imperfecta (OI) or isolated forms without other non-oral phenotypes. Mutations in the gene encoding dentin sialophosphoprotein (DSPP) have been identified to cause dentinogenesis imperfecta (DGI) Types II and III and dentin dysplasia (DD) Type II. While DGI Type I is an OI-related syndromic phenotype caused mostly by monoallelic mutations in the genes encoding collagen type I alpha 1 chain (<i>COL1A1</i>) and collagen type I alpha 2 chain (<i>COL1A2</i>). In this study, we recruited families with non-syndromic dentin defects and performed candidate gene sequencing for <i>DSPP</i> exons and exon/intron boundaries. Three unrelated Korean families were further analyzed by whole-exome sequencing due to the lack of the <i>DSPP</i> mutation, and heterozygous <i>COL1A2</i> mutations were identified: c.3233G>A, p.(Gly1078Asp) in Family 1 and c.1171G>A, p.(Gly391Ser) in Family 2 and 3. Haplotype analysis revealed different disease alleles in Families 2 and 3, suggesting a mutational hotspot. We suggest expanding the molecular genetic etiology to include <i>COL1A2</i> for isolated dentin defects in addition to <i>DSPP</i>.https://www.mdpi.com/2075-4426/11/6/526hereditarymutational hotspotdentinogenesis imperfectaisolated dentin defecttoothdiscoloration |
| spellingShingle | Yejin Lee Youn Jung Kim Hong-Keun Hyun Jae-Cheoun Lee Zang Hee Lee Jung-Wook Kim Non-Syndromic Dentinogenesis Imperfecta Caused by Mild Mutations in <i>COL1A2</i> Journal of Personalized Medicine hereditary mutational hotspot dentinogenesis imperfecta isolated dentin defect tooth discoloration |
| title | Non-Syndromic Dentinogenesis Imperfecta Caused by Mild Mutations in <i>COL1A2</i> |
| title_full | Non-Syndromic Dentinogenesis Imperfecta Caused by Mild Mutations in <i>COL1A2</i> |
| title_fullStr | Non-Syndromic Dentinogenesis Imperfecta Caused by Mild Mutations in <i>COL1A2</i> |
| title_full_unstemmed | Non-Syndromic Dentinogenesis Imperfecta Caused by Mild Mutations in <i>COL1A2</i> |
| title_short | Non-Syndromic Dentinogenesis Imperfecta Caused by Mild Mutations in <i>COL1A2</i> |
| title_sort | non syndromic dentinogenesis imperfecta caused by mild mutations in i col1a2 i |
| topic | hereditary mutational hotspot dentinogenesis imperfecta isolated dentin defect tooth discoloration |
| url | https://www.mdpi.com/2075-4426/11/6/526 |
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