دورية أكاديمية
Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome.
| العنوان: | Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome. |
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| المؤلفون: | Meester JAN; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium., Hebert A; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium., Bastiaansen M; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium., Rabaut L; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium., Bastianen J; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium., Boeckx N; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium., Ashcroft K; Department of Clinical Genetics, Chapel Allerton Hospital, Leeds Teaching Hospitals, NHS Foundation Trust, Leeds, UK., Atwal PS; Genomic and Personalized Medicine, Atwal Clinic, Palm Beach, FL, USA., Benichou A; Department of Internal and Vascular Medicine, CHU Nantes, Nantes Université, Nantes, France., Billon C; Service de Médecine Génomique des Maladies Rares, Groupe Hospitalier Universitaire Centre, Paris, Assistance Publique Hôpitaux de Paris, Paris, France.; Université de Paris Cité, Inserm, PARCC, Paris, France., Blankensteijn JD; Department of Vascular Surgery, Amsterdam University Medical Center, Amsterdam, The Netherlands., Brennan P; Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Bucks SA; GeneDx LLC, Gaithersburg, MD, USA., Campbell IM; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Conrad S; Service de Génétique Médicale, CHU Nantes, Nantes, France., Curtis SL; Bristol Heart Institute, University Hospitals Bristol & Weston NHS Foundation Trust, Bristol, UK., Dasouki M; Department of Medical Genetics & Genomics, AdventHealth Medical Group, Orlando, FL, USA., Dent CL; South West Genomic Laboratory Hub, Bristol Genetics Laboratory, Bristol, UK., Eden J; North West Genomic Laboratory Hub, Manchester Centre for Genomic Medicine, Manchester, UK., Goel H; Hunter Genetics, Waratah, NSW, Australia., Hartill V; Department of Clinical Genetics, Chapel Allerton Hospital, Leeds Teaching Hospitals, NHS Foundation Trust, Leeds, UK.; Leeds Institute of Medical Research, University of Leeds, Leeds, UK., Houweling AC; Department of Human Genetics, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Isidor B; Service de Génétique Médicale, CHU Nantes, Nantes, France., Jackson N; Clinical Genetics Service, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK., Koopman P; Department of Cardiology, Heart Centre Hasselt, Jessa Hospital, Hasselt, Belgium., Korpioja A; Department of Clinical Genetics, Research Unit of Clinical Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland., Kraatari-Tiri M; Department of Clinical Genetics, Research Unit of Clinical Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland., Kuulavainen L; Department of Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Lee K; Department of Medical Genetics & Genomics, AdventHealth Medical Group, Orlando, FL, USA., Low KJ; Clinical Genetics Department, University Hospitals Bristol and Weston NHS Foundation Trust St Michael's Hospital, Bristol, UK.; University of Bristol, Canynge Hall, Bristol, UK., Lu AC; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., McManus ML; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Oakley SP; John Hunter Hospital, New Lambton Heights, NSW, Australia.; College of Health, Medicine and Wellbeing, School of Medicine, University of Newcastle, Newcastle, NSW, Australia., Oliver J; Genomic Diagnostics Laboratory, Manchester Centre for Genomic Medicine, Manchester, UK., Organ NM; John Hunter Hospital, New Lambton Heights, NSW, Australia., Overwater E; Department of Human Genetics, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands., Revencu N; Center for Human Genetics, Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium., Trainer AH; Department of Genomic Medicine, The Royal Melbourne Hospital and University of Melbourne, Parkville, Melbourne, VIC, Australia., Trivedi B; Department of Medical Genetics & Genomics, AdventHealth Medical Group, Orlando, FL, USA., Turner CLS; Department of Clinical Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK., Whittington R; South West Genomic Laboratory Hub, Bristol Genetics Laboratory, Bristol, UK., Zankl A; Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.; Department of Clinical Genetics, Children's Hospital at Westmead, Sydney, NSW, Australia.; Garvan Institute of Medical Research, Sydney, NSW, Australia., Zentner D; Department of Genomic Medicine, The Royal Melbourne Hospital and University of Melbourne, Parkville, Melbourne, VIC, Australia., Van Laer L; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium., Verstraeten A; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium., Loeys BL; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium. bart.loeys@uantwerpen.be.; Department of Clinical Genetics, Radboud University Medical Center, Nijmegen, The Netherlands. bart.loeys@uantwerpen.be. |
| المصدر: | NPJ genomic medicine [NPJ Genom Med] 2024 Mar 26; Vol. 9 (1), pp. 22. Date of Electronic Publication: 2024 Mar 26. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Nature in partnership with the Center of Excellence in Genomic Medicine Research at King Abdulaziz University Country of Publication: England NLM ID: 101685193 Publication Model: Electronic Cited Medium: Internet ISSN: 2056-7944 (Electronic) Linking ISSN: 20567944 NLM ISO Abbreviation: NPJ Genom Med Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Publication: 2016- : [London] : Springer Nature in partnership with the Center of Excellence in Genomic Medicine Research at King Abdulaziz University Original Publication: [London] : Nature Publishing Group, published in partnership with Center of Excellence in Genomic Medicine Research, [2016]- |
| مستخلص: | Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females). The identified BGN variants were shown to lead to loss-of-function by cDNA and Western Blot analyses of skin fibroblasts or were strongly predicted to lead to loss-of-function based on the nature of the variant. No (likely) pathogenic missense variants without additional (predicted) splice effects were identified. Interestingly, a male proband with a deletion spanning the coding sequence of BGN and the 5' untranslated region of the downstream gene (ATP2B3) presented with a more severe skeletal phenotype. This may possibly be explained by expressional activation of the downstream ATPase ATP2B3 (normally repressed in skin fibroblasts) driven by the remnant BGN promotor. This study highlights that aneurysms and dissections in MRLS extend beyond the thoracic aorta, affecting the entire arterial tree, and cardiovascular symptoms may coincide with non-specific connective tissue features. Furthermore, the clinical presentation is more severe and penetrant in males compared to females. Extensive analysis at RNA, cDNA, and/or protein level is recommended to prove a loss-of-function effect before determining the pathogenicity of identified BGN missense and non-canonical splice variants. In conclusion, distinct mechanisms may underlie the wide phenotypic spectrum of MRLS patients carrying loss-of-function variants in BGN. (© 2024. The Author(s).) |
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| معلومات مُعتمدة: | K08 HD111688 United States HD NICHD NIH HHS |
| تواريخ الأحداث: | Date Created: 20240327 Latest Revision: 20240416 |
| رمز التحديث: | 20240416 |
| مُعرف محوري في PubMed: | PMC10966070 |
| DOI: | 10.1038/s41525-024-00413-z |
| PMID: | 38531898 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2056-7944 |
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| DOI: | 10.1038/s41525-024-00413-z |