Whole exome sequencing identified a novel compound heterozygous variation in COL7A1 gene causing dystrophic epidermolysis bullosa
Abstract Dystrophic epidermolysis bullosa (DEB) is a series of severe genetic conditions affecting skin and nails caused by mutations in the COL7A1 gene. DEB has a strong phenotypic variability. In the present study, we recruited a case with a boy exhibiting typical DEB indication, and performed a c...
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| Format: | Article |
| Language: | English |
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Wiley
2022-05-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1907 |
| _version_ | 1811288024794791936 |
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| author | Li‐min Cui Jian‐ye Jiang Ning‐ning Hu Hong‐en Zou Bao‐zhen Zhao Cong‐ying Han Kai Yang Yi‐peng Wang Huan‐xia Xing |
| author_facet | Li‐min Cui Jian‐ye Jiang Ning‐ning Hu Hong‐en Zou Bao‐zhen Zhao Cong‐ying Han Kai Yang Yi‐peng Wang Huan‐xia Xing |
| author_sort | Li‐min Cui |
| collection | DOAJ |
| description | Abstract Dystrophic epidermolysis bullosa (DEB) is a series of severe genetic conditions affecting skin and nails caused by mutations in the COL7A1 gene. DEB has a strong phenotypic variability. In the present study, we recruited a case with a boy exhibiting typical DEB indication, and performed a clinical, genetic, and experimental investigation, followed by a prenatal diagnosis on their current pregnancy. Whole exome sequencing identified a novel compound heterozygous variation in COL7A1, consisting of two variants, namely c.191T>C (p.Leu64Pro) and c.5124G>A (p.Leu1708=) in the proband. In vitro study by minigene system indicated that c.5124G>A would result in an increased ratio of a transcript with exon‐skipping, which supported its pathogenicity. Further prenatal detection confirmed the genotype–phenotye co‐separation in this family. In conclusion, the findings in our study expanded the mutation spectrum of DEB, and emphasized the importance of paying attention to specific synonymous variants in the filtering process. |
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| format | Article |
| id | doaj.art-d6bb768a353f4d8cb5696e1df4841e8d |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-13T03:29:58Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-d6bb768a353f4d8cb5696e1df4841e8d2022-12-22T03:04:32ZengWileyMolecular Genetics & Genomic Medicine2324-92692022-05-01105n/an/a10.1002/mgg3.1907Whole exome sequencing identified a novel compound heterozygous variation in COL7A1 gene causing dystrophic epidermolysis bullosaLi‐min Cui0Jian‐ye Jiang1Ning‐ning Hu2Hong‐en Zou3Bao‐zhen Zhao4Cong‐ying Han5Kai Yang6Yi‐peng Wang7Huan‐xia Xing8Prenatal Diagnosis Center, Langfang Maternal and Child Health Care Hospital Langfang ChinaPrenatal Diagnosis Center, Langfang Maternal and Child Health Care Hospital Langfang ChinaPrenatal Diagnosis Center, Langfang Maternal and Child Health Care Hospital Langfang ChinaPrenatal Diagnosis Center, Langfang Maternal and Child Health Care Hospital Langfang ChinaPrenatal Diagnosis Center, Langfang Maternal and Child Health Care Hospital Langfang ChinaPrenatal Diagnosis Center, Langfang Maternal and Child Health Care Hospital Langfang ChinaPrenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing ChinaPrenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing ChinaPrenatal Diagnosis Center, Langfang Maternal and Child Health Care Hospital Langfang ChinaAbstract Dystrophic epidermolysis bullosa (DEB) is a series of severe genetic conditions affecting skin and nails caused by mutations in the COL7A1 gene. DEB has a strong phenotypic variability. In the present study, we recruited a case with a boy exhibiting typical DEB indication, and performed a clinical, genetic, and experimental investigation, followed by a prenatal diagnosis on their current pregnancy. Whole exome sequencing identified a novel compound heterozygous variation in COL7A1, consisting of two variants, namely c.191T>C (p.Leu64Pro) and c.5124G>A (p.Leu1708=) in the proband. In vitro study by minigene system indicated that c.5124G>A would result in an increased ratio of a transcript with exon‐skipping, which supported its pathogenicity. Further prenatal detection confirmed the genotype–phenotye co‐separation in this family. In conclusion, the findings in our study expanded the mutation spectrum of DEB, and emphasized the importance of paying attention to specific synonymous variants in the filtering process.https://doi.org/10.1002/mgg3.1907COL7A1 genedystrophic epidermolysis bullosaminigene systemwhole exome sequencing |
| spellingShingle | Li‐min Cui Jian‐ye Jiang Ning‐ning Hu Hong‐en Zou Bao‐zhen Zhao Cong‐ying Han Kai Yang Yi‐peng Wang Huan‐xia Xing Whole exome sequencing identified a novel compound heterozygous variation in COL7A1 gene causing dystrophic epidermolysis bullosa Molecular Genetics & Genomic Medicine COL7A1 gene dystrophic epidermolysis bullosa minigene system whole exome sequencing |
| title | Whole exome sequencing identified a novel compound heterozygous variation in COL7A1 gene causing dystrophic epidermolysis bullosa |
| title_full | Whole exome sequencing identified a novel compound heterozygous variation in COL7A1 gene causing dystrophic epidermolysis bullosa |
| title_fullStr | Whole exome sequencing identified a novel compound heterozygous variation in COL7A1 gene causing dystrophic epidermolysis bullosa |
| title_full_unstemmed | Whole exome sequencing identified a novel compound heterozygous variation in COL7A1 gene causing dystrophic epidermolysis bullosa |
| title_short | Whole exome sequencing identified a novel compound heterozygous variation in COL7A1 gene causing dystrophic epidermolysis bullosa |
| title_sort | whole exome sequencing identified a novel compound heterozygous variation in col7a1 gene causing dystrophic epidermolysis bullosa |
| topic | COL7A1 gene dystrophic epidermolysis bullosa minigene system whole exome sequencing |
| url | https://doi.org/10.1002/mgg3.1907 |
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