Rare syndromic craniosynostosis or isolated multisuture synostosis
Gene: ACTB
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 5 Mar 2022, 6:18 p.m. | Last Modified: 5 Mar 2022, 6:18 p.m.
Panel Version: 2.65
Comment on list classification: Promoting from grey to amber, but with a recommendation for green rating following GMS review. There are more than 3 cases with plausible disease causing variants in this gene, and a relevant phenotype.Created: 22 Jul 2021, 11:49 a.m. | Last Modified: 22 Jul 2021, 11:49 a.m.
Panel Version: 2.28
Associated with Baraitser-Winter syndrome 1 #243310 (AD) in OMIM.
More than 3 cases reported that include a craniosynostosis phenotype including:
PMID: 22366783 - Rivière et al 2012 - report 10 patients with Baraitser-Winter syndrome and variants in ACTB. 4 different missense variants were detected. In 4 cases they were shown to be de novo. No parental DNA was available in other cases. 8/10 showed trigonocephaly (metopic craniosynostosis). WES was used to screen initial trios and then targetted sequencing was used in further cases.
PMID: 23649928 - Johnston et al 2013 - report a 7 year old girl with atypical Baraitser-Winter syndrome-1 but whose features include metopic ridging. Exome analysis identified a de novo missense variant in ACTB, c.349G>A, p.E117K.
PMID: 23756437 - Donato et al 2014 - report 3 patients who had been diagnosed with Fryns-Aftimos syndrome and found that all 3 have different missense variants in the ACTB gene (targeted sequencing of ACTB and ACTG1). 1 had pansynostosis and 2 others were reported to have trigonocephaly. They reclassified the diagnosis of these patients as severe BRWS.Created: 22 Jul 2021, 11:47 a.m. | Last Modified: 22 Jul 2021, 11:47 a.m.
Panel Version: 2.25
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Baraitser-Winter syndrome 1, OMIM:243310; Baraitser-Winter syndrome 1, MONDO:0009470
Publications
Ridged metopic suture is a key feature of this condition.
Sources: Expert listCreated: 2 Jul 2020, 10:26 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Baraitser-Winter syndrome 1, MIM# 243310
Tag Q3_21_rating was removed from gene: ACTB.
Source Expert Review Green was added to ACTB. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: actb has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: ACTB were changed from Baraitser-Winter syndrome 1, MIM# 243310 to Baraitser-Winter syndrome 1, OMIM:243310; Baraitser-Winter syndrome 1, MONDO:0009470
Publications for gene: ACTB were set to
Tag missense tag was added to gene: ACTB. Tag Q3_21_rating tag was added to gene: ACTB.
gene: ACTB was added gene: ACTB was added to Craniosynostosis. Sources: Expert list Mode of inheritance for gene: ACTB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: ACTB were set to Baraitser-Winter syndrome 1, MIM# 243310 Review for gene: ACTB was set to GREEN