A pathogenic COL7A1 variant highlights semi-dominant inheritance in dystrophic epidermolysis bullosa
Abstract Dystrophic epidermolysis bullosa is a rare subtype of inherited epidermolysis bullosa, caused by variants in the collagen type VII alpha 1 chain (COL7A1) gene (MIM120120). Both autosomal dominant and recessive inheritance has been reported with variable phenotype. We investigated a Pakistan...
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BMC
2025-02-01
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| Series: | BMC Medical Genomics |
| Online Access: | https://doi.org/10.1186/s12920-024-02077-1 |
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| author | Saira Sattar Thashi Bharadwaj Umm-e- Kalsoom Anushree Acharya Saadullah Khan Suzanne M. Leal Isabelle Schrauwen |
| author_facet | Saira Sattar Thashi Bharadwaj Umm-e- Kalsoom Anushree Acharya Saadullah Khan Suzanne M. Leal Isabelle Schrauwen |
| author_sort | Saira Sattar |
| collection | DOAJ |
| description | Abstract Dystrophic epidermolysis bullosa is a rare subtype of inherited epidermolysis bullosa, caused by variants in the collagen type VII alpha 1 chain (COL7A1) gene (MIM120120). Both autosomal dominant and recessive inheritance has been reported with variable phenotype. We investigated a Pakistani family with dystrophic epidermolysis bullosa via exome sequencing and identified a pathogenic nonsense variant in COL7A1 NM_000094 c.1573 C > T:p.(Arg525*). The inheritance pattern observed was consistent with a semi-dominant model, where heterozygous parents exhibited a mild phenotype, and homozygous children were more severely affected. For dystrophic epidermolysis bullosa, loss-of-function variants are typically associated with the autosomal recessive form, while missense variants are linked to the autosomal dominant form. A review of the literature suggests a semi-dominance pattern for some missense variants, particularly glycine substitutions, but this concept had not been formally recognized. This study highlights the importance of considering semi-dominant inheritance models for dystrophic epidermolysis bullosa and other Mendelian diseases with an autosomal recessive mode of inheritance, as it can significantly impact diagnosis and genetic counseling. |
| format | Article |
| id | doaj-art-e261797ae6154238b7b67bbcdc55aa20 |
| institution | Kabale University |
| issn | 1755-8794 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | BMC Medical Genomics |
| spelling | doaj-art-e261797ae6154238b7b67bbcdc55aa202025-02-09T12:58:52ZengBMCBMC Medical Genomics1755-87942025-02-011811710.1186/s12920-024-02077-1A pathogenic COL7A1 variant highlights semi-dominant inheritance in dystrophic epidermolysis bullosaSaira Sattar0Thashi Bharadwaj1Umm-e- Kalsoom2Anushree Acharya3Saadullah Khan4Suzanne M. Leal5Isabelle Schrauwen6Department of Biochemistry, Hazara UniversityCenter for Statistical Genetics, Gertrude H. Sergievsky Center, Department of Neurology, Columbia University Medical CenterDepartment of Biochemistry, Hazara UniversityCenter for Statistical Genetics, Gertrude H. Sergievsky Center, Department of Neurology, Columbia University Medical CenterDepartment of biotechnology and genetic engineering, Kohat University of sciences and technologyCenter for Statistical Genetics, Gertrude H. Sergievsky Center, Department of Neurology, Columbia University Medical CenterCenter for Statistical Genetics, Gertrude H. Sergievsky Center, Department of Neurology, Columbia University Medical CenterAbstract Dystrophic epidermolysis bullosa is a rare subtype of inherited epidermolysis bullosa, caused by variants in the collagen type VII alpha 1 chain (COL7A1) gene (MIM120120). Both autosomal dominant and recessive inheritance has been reported with variable phenotype. We investigated a Pakistani family with dystrophic epidermolysis bullosa via exome sequencing and identified a pathogenic nonsense variant in COL7A1 NM_000094 c.1573 C > T:p.(Arg525*). The inheritance pattern observed was consistent with a semi-dominant model, where heterozygous parents exhibited a mild phenotype, and homozygous children were more severely affected. For dystrophic epidermolysis bullosa, loss-of-function variants are typically associated with the autosomal recessive form, while missense variants are linked to the autosomal dominant form. A review of the literature suggests a semi-dominance pattern for some missense variants, particularly glycine substitutions, but this concept had not been formally recognized. This study highlights the importance of considering semi-dominant inheritance models for dystrophic epidermolysis bullosa and other Mendelian diseases with an autosomal recessive mode of inheritance, as it can significantly impact diagnosis and genetic counseling.https://doi.org/10.1186/s12920-024-02077-1 |
| spellingShingle | Saira Sattar Thashi Bharadwaj Umm-e- Kalsoom Anushree Acharya Saadullah Khan Suzanne M. Leal Isabelle Schrauwen A pathogenic COL7A1 variant highlights semi-dominant inheritance in dystrophic epidermolysis bullosa BMC Medical Genomics |
| title | A pathogenic COL7A1 variant highlights semi-dominant inheritance in dystrophic epidermolysis bullosa |
| title_full | A pathogenic COL7A1 variant highlights semi-dominant inheritance in dystrophic epidermolysis bullosa |
| title_fullStr | A pathogenic COL7A1 variant highlights semi-dominant inheritance in dystrophic epidermolysis bullosa |
| title_full_unstemmed | A pathogenic COL7A1 variant highlights semi-dominant inheritance in dystrophic epidermolysis bullosa |
| title_short | A pathogenic COL7A1 variant highlights semi-dominant inheritance in dystrophic epidermolysis bullosa |
| title_sort | pathogenic col7a1 variant highlights semi dominant inheritance in dystrophic epidermolysis bullosa |
| url | https://doi.org/10.1186/s12920-024-02077-1 |
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