Rare syndromic craniosynostosis or isolated multisuture synostosis
Gene: AXIN2
Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there is one case and supporting evidence from mouse models. Hence, this gene should be rated AMBER.Created: 12 May 2023, 7:52 p.m. | Last Modified: 12 May 2023, 7:52 p.m.
Panel Version: 4.93
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
craniosynostosis, MONDO:0015469
Publications
• A heterozygous variant in AXIN2 was identified in a pair of twins and their father: c.1181G>A; p.(Arg394His). The variant has an allele frequency of 7.69e-4 – too common to be considered likely pathogenic (Xu et al., 2021).
• A child presenting with sagittal craniosynostosis was found to harbour a de novo loss-of-function variant in exon 4 of AXIN2 (c.1045_1046delCT; p.(Leu349fs*24)), which is absent from gnomAD. Alongside craniosynostosis, the patient displayed frontal bossing, high anterior hair line, depressed nasal bridge, bilateral epicanthus, and low set ears (Yilmaz et al., 2018).
• Animal models are available showing craniosynostosis (Lee et al., 2019)Created: 2 Mar 2023, 1:17 p.m. | Last Modified: 2 Mar 2023, 1:17 p.m.
Panel Version: 3.4
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Yilmaz et al 2018 reported heterozygous frameshift variant NM_004655.3;c.1045_1046delCT, p.L349fs*24 in 3 year old patient with sagittal craniosynostosis. ; Review on behalf of GOSH/Tracy LesterCreated: 5 Mar 2019, 11:33 a.m.
Phenotypes
Oligodontia-colorectal cancer syndrome, 604025
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: AXIN2; Suggested initial gene rating: redCreated: 5 Mar 2019, 11:21 a.m.
Phenotypes for gene: AXIN2 were changed from Oligodontia-colorectal cancer syndrome, OMIM:608615 to Oligodontia-colorectal cancer syndrome, OMIM:608615; craniosynostosis, MONDO:0015469
Publications for gene: AXIN2 were set to
Mode of inheritance for gene: AXIN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene: axin2 has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: AXIN2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: AXIN2 were changed from Oligodontia-colorectal cancer syndrome 604025 to Oligodontia-colorectal cancer syndrome, OMIM:608615
Added phenotypes Oligodontia-colorectal cancer syndrome 604025 for gene: AXIN2
gene: AXIN2 was added gene: AXIN2 was added to Craniosynostosis. Sources: NHS GMS Mode of inheritance for gene: AXIN2 was set to