A novel AXIN2 gene mutation in sagittal synostosis

• Published in: American journal of medical genetics. Part A Vol. 176; no. 9; pp. 1976 - 1980
• Main Authors: Yilmaz, Elanur, Mihci, Ercan, Guzel Nur, Banu, Alper, Ozgul M.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2018
• Subjects: Alleles; Axin Protein - genetics; AXIN2; Child, Preschool; Chromosomes, Human, Pair 17; Cranial sutures; craniofacial disorders; Craniosynostoses - diagnosis; Craniosynostoses - genetics; Craniosynostosis; DNA Mutational Analysis; Dysostosis; Fibroblast growth factor receptor 2; Genetic Association Studies - methods; genetics; Genotype; Humans; Karyotype; Loss of Function Mutation; Male; Mutation; Ossification; Pedigree; Phenotype; Point mutation; sagittal synostosis; Signal transduction; Skull; Turkey; Wnt protein; Wnt signaling; Turkey; Wnt signaling; craniosynostosis; genetics; AXIN2; craniofacial disorders; sagittal synostosis
• DOI: 10.1002/ajmg.a.40373
• ISSN: 1552-4825

The bones of the skull are held together by fibrous joints called sutures. Premature fusion of these sutures leads to a pathologic condition called as craniosynostosis. Although at least 50 nuclear genes including FGFR2, TWIST1, TCF12, and SMAD6 were identified as causative of craniosynostosis; only 25% of the patients can be genetically diagnosed. Here, we report a 3‐year‐old Turkish Caucasian boy with sagittal craniosynostosis with a de novo loss‐of‐function mutation in exon 4 of the AXIN2 gene for the first time. The patient has frontal bossing, high anterior hair line, depressed nasal bridge, bilateral epicanthus and low set ears which are correlated with his scaphocephaly. As a negative regulator of the Wnt signaling pathway which is one of the key modulators of craniosynostosis syndrome, it has been shown in model organisms that Axin2 orchestrates the regulation of beta‐catenin especially in the intramembranous ossification process. This clinical report adds value to the literature that AXIN2 gene mutations could be a potential cause in human calvarial malformations, especially for the sagittal synostosis.