X-linked myopia 26 (Myopia 26, MIM #301010), which is caused by the variants of ARR3 (MIM *301770), is characterized by female-limited early-onset high myopia (eo-HM). Clinical characteristics include a tigroid appearance in the fundus and a temporal crescent of the optic nerve head. At present, the limited literature on eo-HM caused by ARR3 mutations shows that its inheritance mode is complex, which brings certain difficulties to pre-pregnancy genetic counseling, pre-implantation genetic diagnosis, and prenatal diagnosis. Here, we investigated the genetic underpinning of a Chinese family with eo-HM. Whole exome sequencing of the proband revealed a novel frameshift mutation in ARR3 (NM_004312, exon10, c.666delC, p. Asn222LysfsTer22). Although the mode of inheritance of the eo-HM family fits the X-linked pattern of ARR3, the phenotypes of three patients deviate from the typical early-onset high myopia. Through X-chromosome inactivation experiments, the patient’s different phenotypes can be precisely explained. In addition, this study not only enhanced the correlation between ARR3 and early-onset high myopia but also provided explanations for different phenotypes, which may inspire follow-up studies. Our results enrich the knowledge of the variant spectrum in ARR3 and provide critical information for preimplantation and prenatal genetic testing, diagnosis, and counseling.

Retinal artery occlusion (RAO), an acute ocular ischemic stroke, is critically linked to cardiovascular and metabolic dysfunction. To elucidate the interplay between lipid metabolism and immune regulation in RAO, we performed an integrated analysis using serum metabolomics, PBMC transcriptomics, and machine learning in 66 patients with RAO and 66 cataract controls. We identified systemic disruptions in fatty acid metabolism, notably elevated levels of long-chain fatty acids (C22:5n-3, C22:2n-6, C22:1n-9), as distinguishing features of RAO. Upon stratifying patients by lipid status, C20:2n-6 emerged as the top biomarker distinguishing dyslipidemic RAO from non-dyslipidemic cases. Multiomics analysis correlated this accumulation with specific immune pathways, particularly Treg modulation. In Treg-like MT-2 cells, C20:2n-6 promoted Treg proliferation and induced the secretion of the anti-inflammatory cytokine IL-10, independent of TGF-β. These findings highlight C20:2n-6 as a candidate biomarker and implicate the C20:2n-6–Treg–IL-10 axis as a therapeutic target for restoring immune homeostasis in dyslipidemia-associated RAO.