دورية أكاديمية
Osteoporosis related to WNT1 variants: a not infrequent cause of osteoporosis.
| العنوان: | Osteoporosis related to WNT1 variants: a not infrequent cause of osteoporosis. |
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| المؤلفون: | Peris P; Department of Rheumatology, Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain. pperis@clinic.cat., Monegal A; Department of Rheumatology, Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain., Mäkitie RE; Folkhälsan Institute of Genetics, University of Helsinki, P.O. Box 63, FIN-00014, Helsinki, Finland., Guañabens N; Department of Rheumatology, Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain., González-Roca E; Department of Immunology, Hospital Clínic, University of Barcelona, Barcelona, Spain.; Department of Molecular Biology, CORE Laboratory, Hospital Clínic, University of Barcelona, Barcelona, Spain. |
| المصدر: | Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA [Osteoporos Int] 2023 Feb; Vol. 34 (2), pp. 405-411. Date of Electronic Publication: 2022 Nov 18. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer International Country of Publication: England NLM ID: 9100105 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1433-2965 (Electronic) Linking ISSN: 0937941X NLM ISO Abbreviation: Osteoporos Int Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London, UK : Springer International, c1990- |
| مواضيع طبية MeSH: | Osteoporosis*/genetics , Osteoporosis*/drug therapy , Wnt1 Protein*/genetics, Humans ; Diphosphonates/therapeutic use ; Humeral Fractures ; Mutation ; Osteogenesis Imperfecta/complications ; Osteogenesis Imperfecta/genetics ; Osteogenesis Imperfecta/diagnosis ; Pseudarthrosis/drug therapy |
| مستخلص: | Nearly 10% of subjects with severe idiopathic osteoporosis present pathogenic WNT1 mutations. Clinical characteristics include a family history of osteoporosis, early adulthood onset, and fragility fractures which may evolve to pseudoarthrosis. WNT1 should be genetically screened in these patients as the phenotype is often variable and therapeutic approaches may differ. Introduction: Recent studies have shown that homozygous WNT1 gene mutations may be related to severe osteoporosis resembling osteogenesis imperfecta (OI). Conversely, heterozygous WNT1 mutations are linked to a milder phenotype of early-onset osteoporosis. Treatment with bisphosphonates is reported to be unsatisfactory. Our aim was to analyze the presence and prevalence of WNT1 mutations and the main associated clinical characteristics in subjects with primary early-onset osteoporosis. Methods: A cohort comprising 56 subjects (aged 19-60 years) with severe, early-onset osteoporosis was screened by massive parallel sequencing with a 23-gene panel. The gene panel included 19 genes known to cause OI (including the WNT1 gene), three genes related to osteoporosis, and the gene related to hypophosphatasia (ALPL). Results: We identified five patients (3 men) with heterozygous WNT1 variants. All presented severe osteoporosis with early fracture onset and a family history of fragility fractures. None presented a characteristic phenotype of OI or skeletal deformities. One patient was previously treated with bisphosphonates, presenting inadequate response to treatment and two developed pseudoarthrosis after upper arm fractures. All subjects were diagnosed in adulthood. Conclusions: Nearly 1/10 adult subjects with severe idiopathic osteoporosis may present pathogenic WNT1 mutations. Clinical characteristics commonly include a family history of osteoporosis, onset in early adulthood, marked decrease in bone mass, and prevalent fractures, particularly vertebral. WNT1 should be genetically screened in these subjects as the phenotype is often variable and the therapeutic approach may differ. The role of WNT1 mutations in the development of pseudoarthrosis should also be elucidated. (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.) |
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| فهرسة مساهمة: | Keywords: Early-onset osteoporosis; Osteogenesis imperfecta; Severe osteoporosis; WNT1 mutations |
| المشرفين على المادة: | 0 (Diphosphonates) 0 (WNT1 protein, human) 0 (Wnt1 Protein) |
| تواريخ الأحداث: | Date Created: 20221117 Date Completed: 20230125 Latest Revision: 20230125 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1007/s00198-022-06609-2 |
| PMID: | 36396825 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1433-2965 |
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| DOI: | 10.1007/s00198-022-06609-2 |