Variants in CFAP410 cause a range of retinal and skeletal phenotypes

Area of Science:

• Genetics
• Ophthalmology
• Skeletal Dysplasias

Background:

• Ciliopathies encompass a spectrum of genetic disorders affecting cilia function.
• These disorders manifest with diverse phenotypes, including retinal degeneration and skeletal abnormalities.

Purpose of the Study:

• To investigate the clinical spectrum and genetic underpinnings of Cilia and Flagella Associated Protein 410 (CFAP410) variants.
• To characterize the ophthalmic and skeletal phenotypes associated with CFAP410 mutations.

Main Methods:

• Retrospective analysis of 49 patients with CFAP410 variants from global ophthalmic centers.
• Clinical phenotyping, including ophthalmic examination and skeletal assessments.
• Structural modeling of disease-associated variants using ChimeraX.

Main Results:

• Common ophthalmic findings include early-onset visual acuity reduction, photophobia, and delayed dark adaptation.
• Cone-rod dystrophy was more prevalent than rod-cone dystrophy.
• Skeletal abnormalities, specifically axial spondylometaphyseal dysplasia (SMDAX), were present in 22.4% of patients.
• Severe phenotypes correlated with variants in conserved leucine-rich regions of CFAP410.

Conclusions:

• CFAP410 variants are associated with a distinct ciliopathy phenotype.
• The spectrum includes retinal dystrophy and skeletal dysplasia, with variant location influencing severity.
• This study expands the understanding of CFAP410's role in human disease.