Nonsyndromic arteriopathy and aortopathy and vascular Ehlers-Danlos syndrome causing COL3A1 variants.
aortic aneurysm and dissection
atypical course
next-generation sequencing
vascular Ehlers-Danlos syndrome
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
revised:
08
03
2022
received:
12
01
2022
accepted:
09
04
2022
pubmed:
12
5
2022
medline:
17
8
2022
entrez:
11
5
2022
Statut:
ppublish
Résumé
Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal dominant genetic disorder characterized by soft connective tissue vulnerability due to dysfunction of Type III collagen and caused by the pathogenic variants in COL3A1 gene. In the era of next-generation sequencing, multiple genes including COL3A1 can be simultaneously analyzed, and among patients suffering from aortopathy even without any other clinical features suggestive of vEDS, pathogenic COL3A1 variants have been increasingly identified. Here, we briefly summarize the characteristics of 12 Japanese patients from 11 families with arteriopathy and pathogenic or likely pathogenic COL3A1 variants in our hospital. Five patients did not have any extra-arterial clinical features, however, the multigene panel testing for hereditary thoracic aortic aneurysm and dissection unexpectedly revealed that two had glycine substitutions in the triple-helical region and three had haploinsufficient type variants in the COL3A1 gene, whose pathogenicities were all classified as pathogenic or likely pathogenic. Further genetic screening and identification of pathogenic variants in patients with nonsyndromic arteriopathy and aortopathy will enable us to develop risk-stratification and management based on the genetic diagnosis.
Identifiants
pubmed: 35543214
doi: 10.1002/ajmg.a.62774
doi:
Substances chimiques
COL3A1 protein, human
0
Collagen Type III
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
2777-2782Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
Beighton, P., Paepe, A. D., Steinmann, B., Tsipouras, P., & Wenstrup, R. J. (1998). Ehlers-Danlos syndromes: Revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). American Journal of Medical Genetics, 77(1), 31-37.
Byers, P. H., Belmont, J., Black, J., Backer, J. D., Frank, M., Jeunemaitre, X., Johnson, D., Pepin, M., Robert, L., Sanders, L., & Wheeldon, N. (2017). Diagnosis, natural history, and management in vascular Ehlers-Danlos syndrome. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, 175(1), 40-47.
Frank, M., Albuisson, J., Ranque, B., Golmard, L., Mazzella, J.-M., Bal-Theoleyre, L., Fauret, A.-L., Mirault, T., Denarie, N., Mousseaux, E., Boutouyrie, P., Fiessinger, J.-N., Emmerich, J., Messas, E., & Jeunemaitre, X. (2015). The type of variants at the COL3A1 gene associates with the phenotype and severity of vascular Ehlers-Danlos syndrome. European Journal of Human Genetics, 23(12), 1657-1664.
Gago-Diaz, M., Blanco-Verea, A., Teixido-Tura, G., Valenzuela, I., Campo, M. D., Borregan, M., Sobrino, B., Amigo, J., Garcia-Dorado, D., Evangelista, A., Carracedo, A., & Brion, M. (2014). Whole exome sequencing for the identification of a new mutation in TGFB2 involved in a familial case of non-syndromic aortic disease. Clinica Chimica Acta, 437, 88-92.
Jondeau, G., Ropers, J., Regalado, E., Braverman, A., Evangelista, A., Teixedo, G., Backer, J. D., Muino-Mosquera, L., Naudion, S., Zordan, C., Morisaki, T., Morisaki, H., Kodolitsch, Y. V., Dupuis-Girod, S., Morris, S. A., Jeremy, R., Odent, S., Ades, L. C., Bakshi, M., … Montalcino Aortic Consortium. (2016). International registry of patients carrying TGFBR1 or TGFBR2 mutations: Results of the MAC (Montalcino aortic consortium). Circulation. Cardiovascular Genetics, 9(6), 548-558.
Kuivaniemi, H., & Tromp, G. (2019). Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases. Gene, 707, 151-171.
Leistritz, D. F., Pepin, M. G., Schwarze, U., & Byers, P. H. (2011). COL3A1 haploinsufficiency results in a variety of Ehlers-Danlos syndrome type IV with delayed onset of complications and longer life expectancy. Genetics in Medicine, 13(8), 717-722.
Lindsay, M. E., Schepers, D., Bolar, N. A., Doyle, J. J., Gallo, E., Fert-Bober, J., Kempers, M. J. E., Fishman, E. K., Chen, Y., Myers, L., Bjeda, D., Oswald, G., Elias, A. F., Levy, H. P., Anderlid, B.-M., Yang, M. H., Bongers, E. M. H. F., Timmermans, J., Braverman, A. C., … Loeys, B. L. (2012). Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nature Genetics, 44(8), 922-927.
Loeys, B. L., Chen, J., Neptune, E. R., Judge, D. P., Podowski, M., Holm, T., Meyers, J., Leitch, C. C., Katsanis, N., Sharifi, N., Xu, F. L., Myers, L. A., Spevak, P. J., Cameron, D. E., Backer, J. D., Hellemans, J., Chen, Y., Davis, E. C., Webb, C. L., … Dietz, H. C. (2005). A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nature Genetics, 37, 275-281.
Malfait, F., Francomano, C., Byers, P., Belmont, J., Berglund, B., Black, J., Bloom, L., Bowen, J. M., Brady, A. F., Burrows, N. P., Castori, M., Cohen, H., Colombi, M., Demirdas, S., Backer, J. D., Paepe, A. D., Fournel-Gigleux, S., Frank, M., Ghali, N., … Tinkle, B. (2017). The 2017 international classification of the Ehlers-Danlos syndromes. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, 175, 8-26.
Malfait, F., Symoens, S., Backer, J. D., Hermanns-Le, T., Sakalihasan, N., Lapiere, C. M., Coucke, P., & Paepe, A. D. (2007). Three arginine to cysteine substitutions in the pro-alpha (I)-collagen chain cause Ehlers-Danlos syndrome with a propensity to arterial rupture in early adulthood. Human Mutation, 28(4), 387-395.
Ouchi, H., Nishi, H., Nakamura, M., Hirakawa, Y., Tanaka, T., Takeda, N., Akai, T., Ohashi, Y., Hoshina, K., Takayama, T., & Nangaku, M. (2019). Vascular Ehlers-Danlos syndrome diagnosed in a patient initiating hemodialysis. Kidney International Reports, 4(11), 1646-1648.
Pepin, M. G., Schwarze, U., Rice, K. M., Liu, M., Leistritz, D., & Byers, P. H. (2014). Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV). Genetics in Medicine, 16, 881-888.
Rehm, H. L. (2013). Disease-targeted sequencing: A cornerstone in the clinic. Nature Reviews Genetics, 14(4), 295-300.
Renard, M., Francis, C., Ghosh, R., Scott, A. F., Witmer, P. D., Ades, L. C., Andelfinger, G. U., Arnaud, P., Boileau, C., Callewaert, B. L., Guo, D., Hanna, N., Lindsay, M. E., Morisaki, H., Morisaki, T., Pachter, N., Robert, L., Laer, L. V., Dietz, H. C., … Backer, J. D. (2018). Clinical validity of genes for heritable thoracic aortic aneurysm and dissection. Journal of the American College of Cardiology, 72(6), 605-615.
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., & Rehm, H. L. (2015). ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17(5), 405-424.
Schepers, D., Tortora, G., Morisaki, H., MacCarrick, G., Lindsay, M., Liang, D., Mehta, S. G., Hague, J., Verhagen, J., Ivd, L., Wessels, M., Detisch, Y., Mv, H., Baas, A., Lichtenbelt, K., Braun, K., Dvd, L., Roos-Hesselink, J., McGillivray, G., … Laer, L. V. (2018). A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3. Human Mutation, 39(5), 621-634.
Schwarze, U., Schievink, W. I., Petty, E., Jaff, M. R., Babovic-Vuksanovic, D., Cherry, K. J., Pepin, M., & Byers, P. H. (2001). Haploinsufficiency for one COL3A1 allele of type III procollagen results in a phenotype similar to the vascular form of Ehlers-Danlos syndrome, Ehlers-Danlos syndrome type IV. American Journal of Human Genetics, 69, 989-1001.
Shendure, J., & Ji, H. (2008). Next-generation DNA sequencing. Nature Biotechnology, 26(10), 1135-1145.
Takeda, N., Inuzuka, R., Maemura, S., Morita, H., Nawata, K., Fujita, D., Taniguchi, Y., Yamauchi, H., Yagi, H., Kato, M., Nishimura, H., Hirata, Y., Ikeda, Y., Kumagai, H., Amiya, E., Hara, H., Fujiwara, T., Akazawa, H., Suzuki, J., … Komuro, I. (2018). Impact of FBN1 gene mutaion types on the progression of aortic disease in patients with Marfan syndrome. Circulation: Genomic and Precision Medicine, 11(6), e002058.
Takeda, N., Inuzuka, R., Yagi, H., Morita, H., Ando, M., Yamauchi, H., Taniguchi, Y., Porto, K. J., Kanaya, T., Ishiura, H., Mitsui, J., Tsuji, S., Toda, T., Ono, M., & Komuro, I. (2021). Clinical impact of copy number variation on the genetic diagnosis of syndromic aortopathies. Circulation: Genomic and Precision Medicine, 14(4), e003458.
Takeda, N., & Komuro, I. (2019). Genetic basis of hereditary thoracic aortic aneurysms and dissections. Journal of Cardiology, 74(2), 136-143.
Takeda, N., Morita, H., Fujita, D., Inuzuka, R., Taniguchi, Y., Imai, Y., Hirata, Y., & Komuro, I. (2015). Congenital contractual arachnodactyly complicated with aortic dilation and dissection: Case report and review of literature. American Journal of Medical Genetics. Part A, 167A(10), 2382-2387.
Tan, L., Li, Z., Zhou, C., Cao, Y., Zhang, L., Li, X., Cianflone, K., Wang, Y., & Wang, D. W. (2017). FBN1 mutations largely contribute to sporadic non-syndromic aortic dissection. Human Molecular Genetics, 26(24), 4814-4822.