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Objective: To accurately verify the pathogenicity of variants of uncertain significance (VUS) in MUT and MMACHC genes through mass spectrometry and silico analysis., Methods: This multicenter retrospective study included 35 participating units (ClinicalTrials.gov ID: NCT06183138). A total of 3,071 newborns (within 7 days of birth) were sorted into carrying pathogenic/likely pathogenic (P/LP) variants and carrying VUS, non-variant groups. Differences in metabolites among the groups were calculated using statistical analyses. Changes in conservatism, free energy, and interaction force of MMUT and MMACHC variants were analyzed using silico analysis., Results: The percentage of those carrying VUS cases was 68.15% (659/967). In the MMUT gene variant, we found that C3, C3/C2, and C3/C0 levels in those carrying the P/LP variant group were higher than those in the non-variant group ( p < 0.000). The conservative scores of those carrying the P/LP variant group were >7. C3, C3/C0, and C3/C2 values of newborns carrying VUS (c.1159A>C and c.1286A>G) were significantly higher than those of the non-variant group and the remaining VUS newborns ( p < 0.005). The conservative scores of c.1159A>C and c.1286A>G calculated by ConSurf analysis were 9 and 7, respectively. Unfortunately, three MMA patients with c.1159A>C died during the neonatal period; their C3, C3/C0, C3/C2, and MMA levels were significantly higher than those of the controls., Conclusion: Common variants of methylmalonic acidemia in the study population were categorized as VUS. In the neonatal period, the metabolic biomarkers of those carrying the P/LP variant group of the MUT gene were significantly higher than those in the non-variant group. If the metabolic biomarkers of those carrying VUS are also significantly increased, combined with silico analysis the VUS may be elevated to a likely pathogenic variant. The results also suggest that mass spectrometry and silico analysis may be feasible screening methods for verifying the pathogenicity of VUS in other inherited metabolic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiao, Shi, Zhang, Li, Ye, Yuan, Miu, Ma, Diao, Su, Li, Li, Zhuang, Wang, Lu, Gu, Zhou, Xiao, Huang, Wei and Hao.)

Aim: To investigate the long-term safety, efficacy, and binocular balance of monovision surgery using Implantable Collamer Lens (ICL) V4c implantation and Femtosecond Laser-Assisted in situ Keratomileusis (FS-LASIK) for the treatment of myopic patients with presbyopia., Methods: This case series study involved 90 eyes of 45 patients (male/female = 19/26; average age:46.27 ± 5.54 years; average follow-up time:48.73 ± 14.65 months) who underwent the aforementioned surgery to treat myopic presbyopes. Data on manifest refraction, corrected distance visual acuity, dominant eye, presbyopic addition, intraocular pressure, and anterior segment biometric parameters were collected. The visual outcomes and binocular balance at 0.4 m, 0.8 m, and 5 m were documented., Results: The safety index for the ICL V4c and FS-LASIK groups were 1.24 ± 0.27 and 1.04 ± 0.20 ( p  = 0.125), respectively. Binocular visual acuity (logmar) for 0.4 m, 0.8 m, and 5 m were -0.03 ± 0.05, -0.03 ± 0.02, and 0.10 ± 0.03 for the ICL V4c group, and -0.02 ± 0.09, -0.01 ± 0.02, and 0.06 ± 0.04 for the FS-LASIK group, respectively. The proportions of all patients with imbalanced vision at 0.4 m, 0.8 m, and 5 m distances were 68.89, 71.11, and 82.22%, respectively (all p  > 0.05 between the two groups). There were significant differences in refraction between the balanced and imbalanced vision for patients at 0.4 m distance (for non-dominant eye spherical equivalent [SE]: -1.14 ± 0.17D and -1.47 ± 0.13D, p  < 0.001), 0.8 m distance (for preoperative ADD:0.90 ± 0.17D and 1.05 ± 0.11D, p  = 0.041), and 5 m distance (for non-dominant SE: -1.13 ± 0.33D and -1.42 ± 0.11D, p  < 0.001)., Conclusion: ICL V4c implantation and FS-LASIK monovision treatment demonstrated good long-term safety and binocular visual acuity at various distances. After the procedure, the imbalanced patients' vision is primarily related to the age-related presbyopia and anisometropia progression caused by the monovision design., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ye, Zhang, Niu, Shi, Wang, Yan, Zhou and Zhao.)