Molecular genetics & genomic medicine · 2025
Identification and Structural Characterization of a Novel COL3A1 Gene Duplication in a Family With Vascular Ehlers-Danlos Syndrome.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Miolo Gianmaria, Machin Piernicola, De Conto Marco, Fortuna Sara, Viglio Simona, Della Puppa Lara, Geremia Silvano, Corona Giuseppe
Аннотация
BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) is caused by alterations in the COL3A1 gene, typically involving missense variants that replace glycine residues. In contrast, short in-frame insertions, deletions, and duplications are rare and pose significant challenges for investigation.
METHODS: The histological examination of vascular tissue from a 26-year-old man, who died from a common iliac artery aneurysm and whose mother died at age 60 from an abdominal aortic dissection, strongly suggested a diagnosis of Ehler-Danlos type IV. Ex vivo collagen phenotype assessment, molecular analysis, and in silico structural studies of type III collagen were subsequently performed.
RESULTS: Ex vivo analysis of the patient's fibroblasts revealed altered collagen synthesis, whereas the molecular testing identified a novel 18-nucleotide in-frame duplication (c.2868_2885dup-GGGTCTTGCAGGACCACC) in the COL3A1 gene, resulting in a six-amino acid insertion, p.(Leu958_Gly963dup). Structural investigation indicated that this duplication led to a local perturbation of the collagen triple helix near a metalloproteinase cleavage site.
CONCLUSION: This study highlights the pathogenic role of a novel in-frame duplication in the COL3A1 gene, demonstrating how this seemingly benign alteration significantly compromises collagen turnover and contributes to the development of vEDS.
METHODS: The histological examination of vascular tissue from a 26-year-old man, who died from a common iliac artery aneurysm and whose mother died at age 60 from an abdominal aortic dissection, strongly suggested a diagnosis of Ehler-Danlos type IV. Ex vivo collagen phenotype assessment, molecular analysis, and in silico structural studies of type III collagen were subsequently performed.
RESULTS: Ex vivo analysis of the patient's fibroblasts revealed altered collagen synthesis, whereas the molecular testing identified a novel 18-nucleotide in-frame duplication (c.2868_2885dup-GGGTCTTGCAGGACCACC) in the COL3A1 gene, resulting in a six-amino acid insertion, p.(Leu958_Gly963dup). Structural investigation indicated that this duplication led to a local perturbation of the collagen triple helix near a metalloproteinase cleavage site.
CONCLUSION: This study highlights the pathogenic role of a novel in-frame duplication in the COL3A1 gene, demonstrating how this seemingly benign alteration significantly compromises collagen turnover and contributes to the development of vEDS.