Retinal disorders

Gene: FRMD7

This gene is proposed for green rating based on sufficient evidence for the association of FRMD7 variants with foveal hypoplasia. However, expert review is sought from NHS Genomic Laboratory Hubs on the relevance of this phenotype to the scope of retinal disorders panel.

Created: 4 Nov 2025, 12:27 p.m. | Last Modified: 4 Nov 2025, 12:27 p.m.

Panel Version: 8.60

Comment on phenotypes: OMIM accessed on 04 November 2025.

Created: 4 Nov 2025, 12:24 p.m. | Last Modified: 4 Nov 2025, 12:24 p.m.

Panel Version: 8.60

I don't know

FRMD7 variants have been associated with Nystagmus 1, congenital, X-linked (OMIM:310700) and it is a definitive G2P gene for the same condition. In a multicenter study of the Genotypic and Phenotypic Spectrum of Foveal Hypoplasia (FH), Kuht et al (PMID: 35157951) report that FRMD7 variants are associated with 3.5% of the FH cases in the study population (a total of 17 FRMD7 variants are recorded in this study - supplementary file 4). This study also revealed that FRMD7 variants are involved in grade 1 FH or normal foveal morphology and consequently with a good visual acuity in the patients. It was postulated that this maybe due to the delayed action of the FRMD7 variants during development.

Created: 11 Nov 2024, 5:44 p.m. | Last Modified: 11 Nov 2024, 5:55 p.m.

Panel Version: 7.1

Publications

• 35157951

Comment on list classification: New gene added by Mohammed Derar (University of Leeds). This gene is associated with a disease in OMIM and Gene2Phenotype.

PMID: 35157951 found patients with FRMD7 variants had grade 1 foveal hypoplasia or normal foveal morphology.

PMID: 30025138 did not perform any tests to look at foveal hypoplasia.

PMID: 33531592 showed a an FRMD7 variant in one sibling (proband) of a dizygotic twin pair. The other sibling is unaffected. The family reported nystagmus in another male sibling and the maternal grandfather; however, it is unclear whether these two individuals were also tested for FRMD7 variant. The proband had foveal hypoplasia. As it does not appear all patients with variants

PMID: 30015830 identified causative variants in two brothers from a Chinese family who had been diagnosed with idiopathic congenital nystagmus. Retinal OCT was conducted and was found to be normal.

Nystagmus is the presenting feature and foveal hypoplasia does not appear to affect all individuals with FRMD7 variants. This gene is already Green on the "Albinism or congenital nystagmus" (version 1.23) panel; therefore, this gene will remain as Amber for now.

Created: 25 May 2022, 9:27 a.m. | Last Modified: 26 May 2022, 7:28 a.m.

Panel Version: 2.273

Green List (high evidence)

Further evidence from a study studing 904 patients with foveal hypoplasia detected FRMD7 variants in 3.5% of the cohort. The phenotype associated with FRMD7 mutations was a grade 1 foveal hypoplasia.

Created: 2 Jul 2024, 5:30 p.m. | Last Modified: 2 Jul 2024, 5:30 p.m.

Panel Version: 5.15

Mutations in FRMD7 are known to cause infantile nystagmus in an X-linked inheritance (Choi et al., 2018). Recently, with the aid of spectral domain OCT, patients with missense, splice site and nonsense variants in FRMD7 showed a shallow foveal pit diagnosed as grade 1foveal hypoplasia (Thomas et al., 2014)
Sources: Literature

Created: 7 Mar 2022, 6:17 p.m. | Last Modified: 2 Jul 2024, 5:22 p.m.

Panel Version: 5.15

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Infantile nystagmus; foveal hypoplasia

Publications

• (Choi et al., 2018) (PMID: 30025138)
• (Thomas et al., 2014) (PMID:24688117)
• (Kuht et al., 2022) (PMID:35157951)