دورية أكاديمية
AXIN1 mutations in nonsyndromic craniosynostosis.
| العنوان: | AXIN1 mutations in nonsyndromic craniosynostosis. |
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| المؤلفون: | Timberlake AT; 1Hansjörg Wyss Department of Plastic Surgery, NYU Langone Medical Center, New York, New York., Hemal K; 1Hansjörg Wyss Department of Plastic Surgery, NYU Langone Medical Center, New York, New York., Gustafson JA; 2Department of Pediatrics, Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, University of Washington, Seattle, Washington., Hao LT; 3Department of Neurosurgery, Harvard Medical School, and Massachusetts General Hospital, Boston, Massachusetts., Valenzuela I; 4Department of Clinical and Molecular Genetics, Rare Disease Unit, Medical Genetics Group, Vall Hebron Research Institute, Barcelona, Spain., Slavotinek A; 5Department of Pediatrics, Division of Medical Genetics, University of California, San Francisco, California.; 8Department of Pediatrics, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Cunningham ML; 2Department of Pediatrics, Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, University of Washington, Seattle, Washington., Kahle KT; 3Department of Neurosurgery, Harvard Medical School, and Massachusetts General Hospital, Boston, Massachusetts., Lifton RP; 6The Rockefeller University, New York, New York; and., Persing JA; 7Department of Surgery, Division of Plastic Surgery, Yale School of Medicine, New Haven, Connecticut. |
| المصدر: | Journal of neurosurgery. Pediatrics [J Neurosurg Pediatr] 2024 Jun 21; Vol. 34 (3), pp. 246-251. Date of Electronic Publication: 2024 Jun 21 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association of Neurological Surgeons Country of Publication: United States NLM ID: 101463759 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1933-0715 (Electronic) Linking ISSN: 19330707 NLM ISO Abbreviation: J Neurosurg Pediatr Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Charlottesville, VA : American Association of Neurological Surgeons, 2004- |
| مواضيع طبية MeSH: | Axin Protein*/genetics , Craniosynostoses*/genetics , Mutation*, Humans ; Male ; Female ; Infant ; Exome Sequencing ; Child, Preschool |
| مستخلص: | Objective: Occurring once in every 2000 live births, craniosynostosis (CS) is the most frequent cranial birth defect. Although the genetic etiologies of syndromic CS cases are well defined, the genetic cause of most nonsyndromic cases remains unknown. Methods: The authors analyzed exome or RNA sequencing data from 876 children with nonsyndromic CS, including 291 case-parent trios and 585 additional probands. The authors also utilized the GeneMatcher platform and the Gabriella Miller Kids First genome sequencing project to identify additional CS patients with AXIN1 mutations. Results: The authors describe 11 patients with nonsyndromic CS harboring rare, damaging mutations in AXIN1, an inhibitor of Wnt signaling. AXIN1 regulates signaling upstream of key mediators of osteoblast differentiation. Three of the 6 mutations identified in trios occurred de novo in the proband, while 3 were transmitted from unaffected parents. Patients with nonsyndromic CS were highly enriched for mutations in AXIN1 compared to both expectation (p = 0.0008) and exome sequencing data from > 76,000 healthy controls (p = 2.3 × 10-6), surpassing the thresholds for genome-wide significance. Conclusions: These findings describe the first phenotype associated with mutations in AXIN1, with mutations identified in approximately 1% of nonsyndromic CS cases. The results strengthen the existing link between Wnt signaling and maintenance of cranial suture patency and have implications for genetic testing in families with CS. |
| فهرسة مساهمة: | Keywords: AXIN1; Wnt signaling; craniofacial; de novo mutations; nonsyndromic craniosynostosis |
| المشرفين على المادة: | 0 (Axin Protein) 0 (AXIN1 protein, human) |
| تواريخ الأحداث: | Date Created: 20240621 Date Completed: 20240902 Latest Revision: 20240902 |
| رمز التحديث: | 20240902 |
| مُعرف محوري في PubMed: | PMC11200303 |
| DOI: | 10.3171/2024.5.PEDS24115 |
| PMID: | 38905707 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1933-0715 |
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| DOI: | 10.3171/2024.5.PEDS24115 |