Aggrecan-related bone disorders; a novel heterozygous ACAN variant associated with spondyloepimetaphyseal dysplasia expanding the phenotypic spectrum and review of literature
Background: Spondyloepimetaphyseal dysplasias (SEMD) are a large group of skeletal disorders represented by abnormalities of vertebrae in addition to epiphyseal and metaphyseal areas of bones. Several genes have been identified underlying different forms. ACAN gene mutations were found to cause Aggr...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Journal of Genetic Engineering and Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1687157X23015123 |
| _version_ | 1827265339328561152 |
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| author | Hoda A. Ahmed R. Elhossini M. Aglan Khalda Amr |
| author_facet | Hoda A. Ahmed R. Elhossini M. Aglan Khalda Amr |
| author_sort | Hoda A. Ahmed |
| collection | DOAJ |
| description | Background: Spondyloepimetaphyseal dysplasias (SEMD) are a large group of skeletal disorders represented by abnormalities of vertebrae in addition to epiphyseal and metaphyseal areas of bones. Several genes have been identified underlying different forms. ACAN gene mutations were found to cause Aggrecan-related bone disorders (spondyloepimetaphyseal dysplasias,spondyloepiphyseal dysplasias, familial osteochondritis dissecans and short stature syndromes). This study aims to find the disease causing variant in Egyptian patient with SEMD using whole exome sequencing. Methods: Whole-exome sequencing was performed for an Egyptian male patient who presented with short stature, clinical and radiological features suggestive of unclassified SEMD. Results: The study identified a novel de novo heterozygous ACAN gene variant (c.7378G>A; p.Gly2460Arg) in G3 domain. Mutations in ACAN gene have been more commonly associated with short stature than SEMD. The phenotype of our patient was intermediate in severity between spondyloepiphyseal dysplasia presentation; Kimberley type(SEDK) and Spondyloepimetaphyseal dysplasias Aggrecan (SEMDAG) Conclusions: Whole exome sequencing revealed a novel de novo ACAN gene variant in patient with SEDK. The clinical and skeletal phenotype of our patient was much severe than those reported originally and showed more metaphyseal involvement. To the best of our knowledge, two previous studies reported a heterozygous variant in ACAN with spondyloepiphyseal dysplasia presentation; Kimberley type. |
| first_indexed | 2024-04-24T23:18:13Z |
| format | Article |
| id | doaj.art-00b93e0917d749ac9c55d23f9a05ade3 |
| institution | Directory Open Access Journal |
| issn | 1687-157X |
| language | English |
| last_indexed | 2025-03-22T04:00:23Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Genetic Engineering and Biotechnology |
| spelling | doaj.art-00b93e0917d749ac9c55d23f9a05ade32024-04-28T10:05:50ZengElsevierJournal of Genetic Engineering and Biotechnology1687-157X2024-03-01221100341Aggrecan-related bone disorders; a novel heterozygous ACAN variant associated with spondyloepimetaphyseal dysplasia expanding the phenotypic spectrum and review of literatureHoda A. Ahmed0R. Elhossini1M. Aglan2Khalda Amr3Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Egypt; Corresponding author at: Researcher of Molecular Genetics, Human Genetics and Genome Research Institute, National Research Centre, Egypt.Department of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, EgyptDepartment of Clinical Genetics, Human Genetics and Genome Research Institute, National Research Centre, EgyptMedical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, EgyptBackground: Spondyloepimetaphyseal dysplasias (SEMD) are a large group of skeletal disorders represented by abnormalities of vertebrae in addition to epiphyseal and metaphyseal areas of bones. Several genes have been identified underlying different forms. ACAN gene mutations were found to cause Aggrecan-related bone disorders (spondyloepimetaphyseal dysplasias,spondyloepiphyseal dysplasias, familial osteochondritis dissecans and short stature syndromes). This study aims to find the disease causing variant in Egyptian patient with SEMD using whole exome sequencing. Methods: Whole-exome sequencing was performed for an Egyptian male patient who presented with short stature, clinical and radiological features suggestive of unclassified SEMD. Results: The study identified a novel de novo heterozygous ACAN gene variant (c.7378G>A; p.Gly2460Arg) in G3 domain. Mutations in ACAN gene have been more commonly associated with short stature than SEMD. The phenotype of our patient was intermediate in severity between spondyloepiphyseal dysplasia presentation; Kimberley type(SEDK) and Spondyloepimetaphyseal dysplasias Aggrecan (SEMDAG) Conclusions: Whole exome sequencing revealed a novel de novo ACAN gene variant in patient with SEDK. The clinical and skeletal phenotype of our patient was much severe than those reported originally and showed more metaphyseal involvement. To the best of our knowledge, two previous studies reported a heterozygous variant in ACAN with spondyloepiphyseal dysplasia presentation; Kimberley type.http://www.sciencedirect.com/science/article/pii/S1687157X23015123Skeletal dysplasiasACANHeterozygous |
| spellingShingle | Hoda A. Ahmed R. Elhossini M. Aglan Khalda Amr Aggrecan-related bone disorders; a novel heterozygous ACAN variant associated with spondyloepimetaphyseal dysplasia expanding the phenotypic spectrum and review of literature Journal of Genetic Engineering and Biotechnology Skeletal dysplasias ACAN Heterozygous |
| title | Aggrecan-related bone disorders; a novel heterozygous ACAN variant associated with spondyloepimetaphyseal dysplasia expanding the phenotypic spectrum and review of literature |
| title_full | Aggrecan-related bone disorders; a novel heterozygous ACAN variant associated with spondyloepimetaphyseal dysplasia expanding the phenotypic spectrum and review of literature |
| title_fullStr | Aggrecan-related bone disorders; a novel heterozygous ACAN variant associated with spondyloepimetaphyseal dysplasia expanding the phenotypic spectrum and review of literature |
| title_full_unstemmed | Aggrecan-related bone disorders; a novel heterozygous ACAN variant associated with spondyloepimetaphyseal dysplasia expanding the phenotypic spectrum and review of literature |
| title_short | Aggrecan-related bone disorders; a novel heterozygous ACAN variant associated with spondyloepimetaphyseal dysplasia expanding the phenotypic spectrum and review of literature |
| title_sort | aggrecan related bone disorders a novel heterozygous acan variant associated with spondyloepimetaphyseal dysplasia expanding the phenotypic spectrum and review of literature |
| topic | Skeletal dysplasias ACAN Heterozygous |
| url | http://www.sciencedirect.com/science/article/pii/S1687157X23015123 |
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