| Autor: |
Gensemer C, Beck T, Guo L, Petrucci T, Morningstar J, Kornblau I, Byerly K, Biggs R, Weintraub A, Moore K, Koren N, Daylor V, Hastings C, Oberlies E, Zientara ER, Devey E, Dooley S, Stayer K, Fenner R, Singleton K, Luzbetak S, Bear D, Byrd R, Weninger J, Bistran E, Beeson G, Kerns J, Griggs M, Griggs C, Osterhaus M, Fleck E, Schnaudigel J, Butler S, Severance S, Kendall W, Delaney JR, Judge DP, Chen P, Yao H, Guz J, Awgulewitsch A, Kautz SA, Mukherjee R, Price R, Henderson F Sr, Shapiro S, Francomano CA, Kovacic JC, Lavallee M, Patel S, Berrandou TE, Slaugenhaupt SA, Milan D, Kontorovich AR, Bouatia-Naji N, Norris RA; Medical University of South Carolina. |
| Jazyk: |
angličtina |
| Zdroj: |
Research square [Res Sq] 2024 Jun 10. Date of Electronic Publication: 2024 Jun 10. |
| DOI: |
10.21203/rs.3.rs-4547888/v1 |
| Abstrakt: |
Hypermobile Ehlers-Danlos syndrome (hEDS) is a common heritable connective tissue disorder that lacks a known genetic etiology. To identify genetic contributions to hEDS, whole exome sequencing was performed on families and a cohort of sporadic hEDS patients. A missense variant in Kallikrein-15 (KLK15 p. Gly226Asp), segregated with disease in two families and genetic burden analyses of 197 sporadic hEDS patients revealed enrichment of variants within the Kallikrein gene family. To validate pathogenicity, the variant identified in familial studies was used to generate knock-in mice. Consistent with our clinical cohort, Klk15 G224D/+ mice displayed structural and functional connective tissue defects within multiple organ systems. These findings support Kallikrein gene variants in the pathogenesis of hEDS and represent an important step towards earlier diagnosis and better clinical outcomes. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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