Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: RNU12

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:39 p.m. | Last Modified: 24 Feb 2025, 5:39 p.m.

Panel Version: 5.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

This gene has been tagged again for promotion from Amber to Green as there is enough evidence to support a gene-disease association. RNU12 was not previously added as it is a non-coding gene that was not tiered but it has since been added to the tiering pipeline. Therefore it is appropriate to upgrade it to Green status.

Created: 2 Jul 2024, 1:01 p.m. | Last Modified: 2 Jul 2024, 1:01 p.m.

Panel Version: 5.1

Removed 'currently-ngs-unreportable' tag as tiering of non-coding genes including RNU12, has now been added to the Genomics England Rare Disease pipeline. The Ensembl ID for RNU12 has also been added.

Created: 2 Jul 2024, 12:52 p.m. | Last Modified: 2 Jul 2024, 12:52 p.m.

Panel Version: 5.1

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed. It has been agreed that this gene should remain amber at this time.

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 this gene from grey to amber. It could be promoted to green after GMS review as there are 3 unrelated cases with a craniosynostosis phenotype. However, variants in this gene would not currently be reported as it is not a protein coding gene. An Ensembl ID also needs to be added before it is promoted to green.

Created: 28 Jul 2021, 10:09 a.m. | Last Modified: 28 Jul 2021, 10:09 a.m.

Panel Version: 2.50

Note RNU12 has Ensembl gene ID ENSG00000276027 in GRCh38. It is not listed in OMIM.

As reported by expert reviewer PMID: 34085356 (Xing et al 2021) report the analysis of 5 patients from 4 unrelated families with clinical features of CDAGS (Craniosynostosis and clavicular hypoplasia; Delayed closure of the fontanelles and cranial defects (and deafness in some patients); Anal anomalies; Genitourinary malformations; and Skin eruption, including porokeratosis). WES and Sanger sequencing was used to identify rare biallelic variants in RNU12. All affected individuals were compound heterozygous, with all 5 patients sharing NC_000022.10:g.43011402C>T, which alters a highly conserved nucleotide. Each individual also carried another variant (4 different variants) in RNU12 thought to disrupt the secondary structure or the Sm binding site of the RNU12 snRNA. Craniosynostosis was noted in 3 of the families (Family 1 - bilateral coronal synostosis, Family 3 - brachycephaly, wide-open anterior and posterior fontanels, and complete coronal synostosis, Family 4 - brachycephaly)

Created: 28 Jul 2021, 3:33 a.m. | Last Modified: 28 Jul 2021, 3:33 a.m.

Panel Version: 2.48

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
CDAGS syndrome, OMIM:603116; craniosynostosis-anal anomalies-porokeratosis syndrome, MONDO:0011287

Publications

• 34085356

Green List (high evidence)

5 CDAGS syndrome families with biallelic variants all including NC_000022.10:g.43011402C>T and another variant on the second allele. Whole transcriptome sequencing analysis of patient lymphoblastoid cells identified differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events. Craniosynostosis is a major feature of the condition.
Sources: Literature

Created: 8 Jul 2021, 8:37 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
CDAGS syndrome MIM#603116; Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations

Publications

• 34085356