AXIN1 mutations in nonsyndromic craniosynostosis.
J Neurosurg Pediatr
; 34(3): 246-251, 2024 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-38905707
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Craneosinostosis
/
Proteína Axina
/
Mutación
Límite:
Child, preschool
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Female
/
Humans
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Infant
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Male
Idioma:
En
Revista:
J Neurosurg Pediatr
Asunto de la revista:
NEUROCIRURGIA
/
PEDIATRIA
Año:
2024
Tipo del documento:
Article