Rare syndromic craniosynostosis or isolated multisuture synostosis
Gene: ZNF462
Agree with evidence below - promote to green geneCreated: 7 Jan 2022, 2:32 p.m. | Last Modified: 7 Jan 2022, 2:32 p.m.
Panel Version: 2.60
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Weiss Kruszka syndrome
Publications
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
Helen Lord review concurs with proposed green rating.Created: 12 Jan 2022, 2:53 p.m. | Last Modified: 12 Jan 2022, 2:53 p.m.
Panel Version: 2.61
Comment on list classification: Promoting from grey to amber, but with a recommendation for green rating following GMS review. Metopic ridging or craniosynostosis reported in 6 cases with a plausible disease causing variant in ZNF462.Created: 28 Jul 2021, 1:08 a.m. | Last Modified: 28 Jul 2021, 1:08 a.m.
Panel Version: 2.43
Associated with Weiss-Kruszka syndrome #618619 (AD) in OMIM.
PMID: 28513610 - Weiss et al 2017 - report 8 individuals from 6 families with predicted loss of function variants in ZNF462. They have overlapping phenotypes that include ptosis, metopic ridging, craniosynostosis, dysgenesis of the corpus callosum, and developmental delay. Metopic ridging or lambdoid craniosynostosis was noted in 5 of the 8 subjects (from 3 unrelated families). Family 1 had a nonsense variant that segregated in 4 family members with a variable phenotype. In all other families de novo variants or deletions (1.6 and 1.9 MB) in ZNF462 were found.
PMID: 31361404 - Kruszka et al 2019 - report an additional 14 individuals with loss of function variants in ZNF462. Most have some form of developmental delay, ptosis, down slanting palpebral fissures, exaggerated Cupid's bow/wide philtrum, and arched eyebrows. Metopic ridging or craniosynostosis was found in 3/14. In most cases the variant was found to be de novo.Created: 28 Jul 2021, 1:06 a.m. | Last Modified: 28 Jul 2021, 1:06 a.m.
Panel Version: 2.40
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Weiss-Kruszka syndrome, OMIM:618619; weiss-kruszka syndrome, MONDO:0032836
Publications
Craniosynostosis observed in 38% of affected individuals.
Sources: Expert listCreated: 3 Jul 2020, 8:22 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Weiss-Kruszka syndrome, MIM# 618619
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q3_21_rating was removed from gene: ZNF462. Tag Q1_22_NHS_review was removed from gene: ZNF462.
Source Expert Review Green was added to ZNF462. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q1_22_NHS_review tag was added to gene: ZNF462.
Gene: znf462 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: ZNF462 were changed from Weiss-Kruszka syndrome, MIM# 618619 to Weiss-Kruszka syndrome, OMIM:618619; weiss-kruszka syndrome, MONDO:0032836
Publications for gene: ZNF462 were set to 28513610
Tag Q3_21_rating tag was added to gene: ZNF462.
gene: ZNF462 was added gene: ZNF462 was added to Craniosynostosis. Sources: Expert list Mode of inheritance for gene: ZNF462 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZNF462 were set to 28513610 Phenotypes for gene: ZNF462 were set to Weiss-Kruszka syndrome, MIM# 618619 Review for gene: ZNF462 was set to GREEN gene: ZNF462 was marked as current diagnostic