ObjectiveTo investigate and analyze the relationship between genotype and phenotype in patients with early-onset high myopia (eoHM) associated with hereditary eye diseases. MethodsA family-based study was conducted among 30 families diagnosed with eoHM at Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region from January 2022 to June 2023. Seven families (23.3%, 7/30), all probands, and their 14 parents were included. These seven families were unrelated. Detailed patient and family histories were collected. All participants underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, color vision testing, fundus color photography, optical coherence tomography, fluorescein fundus angiography, and fundus autofluorescence imaging. Full-field electroretinography was performed in four cases. Peripheral venous blood samples were collected from patients and their parents for whole-genome DNA extraction and whole-exome sequencing. Potential pathogenic variants were identified, and their pathogenicity was analyzed and confirmed by Sanger sequencing. The pathogenicity of newly discovered gene variants was evaluated according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). Literature on previously reported eoHM associated with hereditary eye diseases was reviewed to analyze the relationship between variant genes and clinical phenotypes. ResultsAmong the seven families, three exhibited X-linked inheritance, two showed autosomal recessive inheritance, and two demonstrated autosomal dominant inheritance. All the patients were male. Among the seven patients, one case each was identified with congenital stationary night blindness (CSNB), Bornholm eye disease, X-linked retinitis pigmentosa (XL-RP), cone-rod dystrophy, Knobloch syndrome, familial exudative vitreoretinopathy (FEVR), and Stickler syndrome. Genetic testing revealed nine gene variants highly correlated with the observed phenotypes. The genetic testing results revealed that all patients were found to carry nine gene variants highly associated with the phenotype, including: a hemizygous missense variant NYX c.647A>T (p.N216I) (M1), an OPN1LW LIAVA haplotype variant (M2), a hemizygous frameshift variant RPGR c.3096_3097del (p.E1033RfsTer45) (M3), compound heterozygous variants TTLL5 c.1588_1589del (p.L531EfsTer24) and c.850G>C (p.D284H) (M4, M5), compound heterozygous variants COL18A1 c.2118dup (p.G707RfsTer23) and c.3523_3524del (p.L1175VfsTer72) (M6, M7), a heterozygous missense mutation FZD4 c.1499C>T (p.T500I) (M8), and a heterozygous frameshift variant COL11A2 c.966dup (p.T323HfsTer19) (M9). Among them, M2, M4, M5, M8 and M9 were newly discovered mutation sites, and M1, M3, M6 and M7 were known mutation sites. According to the classification standards and guidelines of genetic variation issued by ACMG, M2, M3, M4, M6, M7, and M9 were judged to be pathogenic variants, while M1, M5, and M8 were of unknown clinical significance. Through literature review, it was found that eoHM was more common among the clinical phenotypes of 4 types of hereditary retinal diseases, including CSNB, Stickler syndrome, FEVR and XL-RP. ConclusioneoHM is intricately associated with inherited eye diseases and may serve as the earliest indicator of such conditions.
ObjectiveTo investigate the relationship between genotype and phenotype in children with CRB1 mutated Leber congenital amaurosis (LCA) and early onset retinal dystrophy (EOSRD).MethodsA retrospective clinical study. From January 2013 to December 2019, 10 children with CRB1 mutated LCA/EOSRD were enrolled in the study. The patients were identified as CRB1 mutation by the second generation targeted capture sequencing, Sanger sequencing and the family segregation analysis. All children underwent electroretinogram (ERG) and fundus examination. At the same time, 6 cases were examined by optical coherence tomography (OCT); 1 case was examined by fluorescein fundus angiography (FFA), 7 cases were examined by wide-angle laser scanning ophthalmoscope (UWF SLO).ResultsThere were 6 cases of LCA and 4 cases of EOSRD in 10 patients with CRB1 gene mutations. The average age of first visit was 3.61 years old. The light and dark wave of ERG was flat in 6 cases, and decreased in 4 cases. A total of 19 pathogenic mutations were detected. There were 1 homozygous mutation and 9 compound heterozygous mutations. There were 4, 2 and 1 cases of “copper-coin” like, “salt and pepper” like and “osteocyte” like pigment changes in retina, 1 case of “crystalline pigment” change and 2 cases of macular pigment scar. In 7 cases of UWF SLO examination, different degrees of para-arteriolar pigment epithelium retention (PPRPE) were found in the middle and peripheral fundus. In 6 cases examined by OCT, the outer layer of retina atrophied and the band of ellipsoid disappeared. Symmetrical cystoid macular edema, splitting cystoid macular degeneration and adhesion of epi-macular membrane to optic disc and macular area were found in 1 case, respectively, the retinal structure was rough and thickened, and the fovea became thinner in 3 cases. In FFA examination, 1 case showed uveitis-like changes with late optic disc fluorescein staining, macular fluorescence accumulation, strong fluorescence diffusing along the blood vessels in each quadrant, peripheral PPRPE of “frost-branch” like strong fluorescence.ConclusionThe relationship between genotype and phenotype of CRB1 mutation is complex, and PPRPE is a common characteristic change.
ObjectiveThis study aimed to explore the timing of the long-term antiepileptic drugs (AEDs) therapy in patients with stroke related seizures.
MethodsWe enrolled 90 Patients with post-stroke seizures who diagnosed in neurology and epilepsy specialist clinic of Tianjin Medical University General Hospital and followed up for at least 12 months from September 2014 to August 2016. The patients were divided into early-onset seizure group (occurring within 2 weeks of stroke) and late-onset seizure group (occurring after 2 weeks of stroke).The two groups were subdivided into treated and untreated group after the first seizure.
ResultsThe patients were followed up for 12~96m (median 20m). 31 patients in ES group, 19 of which in treated group and 12 of which in untreated group. 59 patients in LS group, 36 of which in treated group and 23 of cases in untreated group. The recurrence rate of second seizures occurred in each group and the comparison between the subgroups in the 3rd, 6th, 9th and 12th mouth of follow-up as follows. 1 LS group compared with the group of ES, the recurrence rate of second seizures was high (25.81%~38.71% vs. 49.15%~69.49%), and there was statistical difference (P < 0.05). 2 The recurrence rate of ES in untreated group was lower than that in untreated LS group (16.77% 33.33% vs. 56.52% 73.91%), but only in 3m and 12m the difference was statistically significant (P < 0.05). 3 There was on statistically significant different in ES treated group compared to untreated group, LS treated group compared to untreated group, ES treated group compared to LS treated group (P > 0.05). Both in group of ES and LS, The ratio of seizure recurred patients at different time points during follow-up period was highest at the time of 3m, 3 6m followed, within six months respectively as high as 91.67% and 76.59%.
ConclusionOnly one early-onset seizure after stroke can be suspended long-term AEDs treatment, once it recurred that indicates the need for treatment. However, the recurrence rate of late-onset seizure was higher than that of early-onset seizure and it should be given long term AEDs treatment after the first seizure.
ObjectiveTo explore the differences in metabolomic changes and metabolic pathways between the vitreous humor and serum of patients with early-onset proliferative diabetic retinopathy (PDR). MethodsA prospective observational study. From January to June 2025, 30 patients with PDR who underwent pars plana vitrectomy (PPV) in the Department of Ophthalmology, Peking University People's Hospital were included in the study. Patients were categorized into an early-onset PDR group (diagnosis age ≤40 years, n=10) and a late-onset PDR group (diagnosis age ＞40 years, n=20) based on the age at diabetes diagnosis. Fasting serum samples collected preoperatively and vitreous humor samples obtained intraoperatively were analyzed using untargeted metabolomics via ultra-high-performance liquid chromatography coupled with electrostatic field orbitrap tandem mass spectrometry. Differential metabolites were screened with thresholds of P＜0.05, variable importance in projection＞1, and fold change＞1.200 or ＜0.833. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). The Mann-Whitney U test was used to compare clinical data between the two groups. ResultsSignificant differences were observed between the early-onset and late-onset PDR groups in the age at diabetes diagnosis and diabetes duration (Z=?4.41, ?2.62; P＜0.05). Metabolomic analysis identified 37 differential metabolites in the vitreous humor (34 upregulated, 3 downregulated) and 42 in the serum (10 upregulated, 32 downregulated). The two most abundant classes of differential metabolites common to both sample types were carboxylic acids and derivatives (16.2% in vitreous, 16.7% in serum) and fatty acyls (13.5% in vitreous, 11.9% in serum). KEGG enrichment analysis revealed the tryptophan metabolism pathway was significantly enriched in the vitreous humor (enrichment factor=0.024, P＜0.05), with L-kynurenine and indole-3-acetamide as key differential metabolites. In the serum, the taurine and hypotaurine metabolism pathway was significantly enriched (enrichment factor=0.042, P＜0.05), with hydroxyethanesulfonic acid identified as a differential metabolite. ConclusionsEarly-onset PDR has characteristic metabolic disorders. The dual activation of the kynurenine and indole branches of tryptophan metabolism in the vitreous humor, alongside increased consumption in the taurine pathway in serum, may underlie its pathophysiology. Additionally, abnormalities in serum steroids and steroid derivatives suggest that dysregulated steroid hormone metabolism might contribute to disease progression.
