Retinal disordersGene: IRX6
Ideally, a region representing the IRX5/IRX6 duplication should be added to PanelApp with a monallelic mode of inheritance. There is a lack of single nucleotide variants reported in this gene with relevance to retinal disorders and and therefore adding this gene as green risks reporting irrelevant SNVs.
Created: 28 Sep 2021, 12:53 p.m. | Last Modified: 28 Sep 2021, 12:53 p.m.
Panel Version: 2.216
Not associated with any disorder in OMIM or Gene2Phenotype.
PMID: 33891002 - Kohl et al 2021 - report 3 unrelated families with duplications of a region covering the genes IRX5 and IRX6 completely, and the proximal exons of MMP2 and cone dystrophy. They propose that overexpression of IRX5 and IRX6 may be the cause of the disease, and this is supported by expression analysis in patient-derived fibroblasts and zebrafish experiments.
Initial family is a large 5 generation German family with 14 members with autosomal dominant cone dystrophy in which a 600kb duplicated region covering IRX5/IRX6 and part of MMP2 was identified. 2 additional families of Chinese and Dutch descent with copy number gains of ~700 and ~850 kb, covering the same region were then identified. The smallest region of overlap is 608kb. In addition another family of German decent is reported with adCD and the same duplication as the first German family. It is not known if they are distantly related. Segregation analysis on available members of all families showed the duplication in affected members and not in unaffected.
They find that IRX5, IRX6 and MMP2 are expressed in human adult retina. Several lincRNA within the locus are also expressed. In patient derived fibroblasts IRX5 and IRX6 showed increased expression levels. Over expression of IRX5 and IRX6 results in impaired visual performance in zebrafish larvae.
Created: 7 Jul 2021, 12:57 p.m. | Last Modified: 8 Jul 2021, 1:37 p.m.
Panel Version: 2.193
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
cone dystrophy, MONDO:0000455
Mode of pathogenicity
Tag Q3_21_rating tag was added to gene: IRX6. Tag Q3_21_expert_review tag was added to gene: IRX6.
Tag cnv tag was added to gene: IRX6.
gene: IRX6 was added gene: IRX6 was added to Retinal disorders. Sources: Literature Mode of inheritance for gene: IRX6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: IRX6 were set to 33891002 Phenotypes for gene: IRX6 were set to cone dystrophy, MONDO:0000455 Mode of pathogenicity for gene: IRX6 was set to Other