Skeletal ciliopathies

Gene: IQCE

Green List (high evidence)

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

Created: 6 Mar 2022, 4:57 p.m. | Last Modified: 6 Mar 2022, 4:57 p.m.

Panel Version: 1.17

Comment on list classification: Promoting from red to amber, but with recommendation of promoting to green following GMS review. 4 cases now reported.

Created: 18 Jan 2021, 4:05 p.m. | Last Modified: 18 Jan 2021, 4:05 p.m.

Panel Version: 1.7

Green Expert Review of this gene on the Limb disorders panel.
PMID: 28488682 Umair et al 2017 report a large consanguineous family of Pakistani origin segregating post-axial polydactyly type A in the feet. A homozygous splice acceptor site variant (c.395-1G>A) was identified by WES in the IQCE gene, which completely co-segregated with the phenotype in the family. They report that the Iqce knockout mouse (MGI:1921489) shows various types of skeletal deformities including pre-axial polydactyly, digit abnormalities, and short and long tibia.

PMID: 31549751 - Estrada-Cuzcano et al 2019 - report 3 families with biallelic pathogenic variations in IQCE identified by WES. The same variant c.895_904del (p.Val301Serfs*8) was found in all families without sharing a common haplotype, suggesting a recurrent mechanism. In one family this variant as compound heterozygous with another IQCE variant p.Glu451Argfs*15. These families with post-axial polydactyly were initially recruited as syndromic ciliopathies and two have additional pathogenic variations in other genes (TULP1 and ATP6V1B1) explaining their apparent syndromic phenotype. Functional studies based on the patient's cells or zebrafish (Danio rerio) assays confirm the ciliary role of IQCE.
Sources: Literature

Created: 18 Jan 2021, 4:04 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Polydactyly, postaxial, type A7 OMIM:617642; polydactyly, postaxial, type a7 MONDO:0060550

Publications

• 28488682
• 31549751