Clefting

Gene: POLR1B

Green List (high evidence)

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

Created: 3 Mar 2022, 4:45 p.m. | Last Modified: 3 Mar 2022, 4:45 p.m.

Panel Version: 2.63

Comment on list classification: Promoting from red to amber but with green recommendation following phenotype review by the GMS. 3 cases reported in which cleft palate was a feature.

Created: 20 Jan 2021, 1:55 p.m. | Last Modified: 20 Jan 2021, 1:56 p.m.

Panel Version: 2.20

Associated with Treacher-Collins syndrome 4 #618939 (AD) in OMIM

PMID: 31649276 - Sanchez et al 2020 - using exome sequencing they identified 6 patients (5 unrelated families) with heterozygous missense variants in POLR1B. In 3 cases the variants were de novo. One was inherited from the mother, and one from the father who was mosaic for the variant. 3 different variants are reported. The clinical phenotype was variable but all patients were reported with downward slanting palpebral fissures, Malar hypoplasia, and Conductive deafness, and 3 individuals from 3 different families had cleft palate. Morphilino knockdown of polr1b showed abnormal craniofacial development of zebrafish embryos
Sources: Literature

Created: 20 Jan 2021, 1:53 p.m. | Last Modified: 20 Jan 2021, 1:54 p.m.

Panel Version: 2.19

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Treacher-Collins syndrome 4 OMIM:618939; treacher collins syndrome 4 MONDO:0030067

Publications

• 31649276