Abstract
AIM: To report two cases of Jalili syndrome (JS) harboring a novel mutation in the CNNM4 gene, review previously published studies on JS, and analyze factors potentially associated with visual acuity in patients with JS. METHODS: Two JS patients from a non-consanguineous Chinese family underwent comprehensive ophthalmic evaluations. Next-generation sequencing (NGS) was performed to identify pathogenic variants, and Sanger sequencing was used for validation. A literature search was conducted to retrieve studies on JS published up to January 31, 2025; only studies with detailed records of visual acuity and mutation sites were included. Correlations between visual acuity and age, as well as between visual acuity and mutation domain, were analyzed. RESULTS: A total of 53 patients with detailed visual acuity and mutation site records from previous studies were included in the analysis. The mean logarithm of the minimum angle of resolution (logMAR) visual acuity was 1.15 (range: 0.69-2.00). Spearman's correlation analysis showed a positive correlation between visual acuity (logMAR) and age (r(s) =0.502, P<0.001). No association was found between logMAR visual acuity and mutation domain (P=0.748). The 6-year-old proband and her 3-year-old brother carried a novel homozygous missense variant c.949A>C (p.Ser317Arg) in CNNM4. Both patients presented with reduced visual acuity, pendular nystagmus, photophobia, night blindness, color vision loss, macular atrophy, and amelogenesis imperfecta. Optical coherence tomography (OCT) revealed atrophy of the outer retinal layers, and electroretinography (ERG) showed extinguished cone and rod responses. Fundus autofluorescence (FAF) and fundus fluorescein angiography (FFA) of the proband demonstrated bilateral retinal pigment epithelium (RPE) defects around the optic disc, vascular arcades, and macular region. At the latest follow-up (30mo), the proband's condition remained stable: best-corrected visual acuity was 2.00 logMAR (right eye) and 1.30 (left eye), with no changes in fundus appearance. The younger brother had a best-corrected visual acuity of 1.52 logMAR in both eyes at the latest follow-up, accompanied by severe bilateral macular atrophy and obvious dentin discoloration due to progressive enamel thinning. CONCLUSION: This study reports a novel homozygous missense variant c.949A>C (p.Ser317Arg) in CNNM4 in a Chinese JS family. Visual acuity in JS patients deteriorates with increasing age.