Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: ASXL3

I don't know

Comment on list classification: As reviewed by Rebecca Tooze (University of Oxford), there are only two cases of craniosynostosis and craniosynostosis was not confirmed in the third case. Hence, this gene should be rated AMBER.

Created: 11 May 2023, 11:39 a.m. | Last Modified: 11 May 2023, 11:39 a.m.

Panel Version: 4.54

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Bainbridge-Ropers syndrome, OMIM:615485; craniosynostosis, MONDO:0015469

Publications

• 24044690
• 33288889

I don't know

• A de novo c.3033dup; p.(Leu1012Serfs*23) was identified in a patient with metopic synostosis within the Norwegian cohort (Tønne et al., 2021).
• A six-year-old with microcephaly, autism, global developmental delay, and metopic craniosynostosis was found on exome sequencing to harbour a heterozygous two base pair de novo deletion, c.1897_1898delCA; p.(Gln633Valfs*13) in ASXL3 (Dinwiddie et al., 2013).
• A heterozygous de novo single nucleotide variant (c.3039+1G>A; p.(?)) in the invariant “GT” splice donor site of exon 11 was identified in an individual with a prominent forehead, thick eyebrows, long lashes, exotropia, depressed nasal ridge, thin upper lip vermillion, hirsutism, microcephaly, bilateral camptodactyly of third, fourth and fifth fingers, deep palmar creases, and small hands and feet. Craniosynostosis is not confirmed (Hori et al., 2016).

Two cases of loss-of-function variants in ASXL3; only one has radiologically confirmed craniosynostosis.
Sources: Literature

Created: 2 Mar 2023, 1:37 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted