Variant in EZR leads to defects in lens development.

BACKGROUND: Congenital cataract is a common cause of blindness. Genetic factors always play important role. MATERIAL AND METHODS: This study identified a novel missense variant (c.1412C>T (p.P471L)) in the EZR gene in a four-generation Chinese family with nuclear cataract by linkage analysis and whole-exome sequencing. A knockout study in zebrafish using transcription activator-like effector nucleases was carried out to gain insight into candidate gene function. RESULTS: Conservative and functional prediction suggests that the P-to-L substitution may impair the function of the human ezrin protein. Histology showed developmental delays in the ezrin-mutated zebrafish, manifesting as multilayered lens epithelial cells. Immunohistochemistry revealed abnormal proliferation patterns in mutant fish. CONCLUSIONS: The study suggests that ezrin may be involved in the enucleation and differentiation of lens epithelial cells.

Management of Contact Lenses and Visual Development in Pediatric Aphakia.

Congenital cataract is among the main causes of treatable vision loss in childhood. The first weeks and months of life are a critical time for the development of vision. Therefore, early cataract surgery and effective multifaceted treatment of the resulting aphakia in the early stages of life are of great value for the management of vision development. Among the treatment models, contact lenses (CL) have an important place in infancy and early childhood up to the age of 2 years. Although good visual gains were not considered very likely, especially in unilateral aphakia, important steps have been taken in the treatment of pediatric aphakia thanks to the surgical techniques developed over time and the increasing experience with optical correction systems, especially CLs. This review examines current developments in the types of CL used in pediatric aphakia, their application features, comparison with other optical systems, the features of amblyopia treatment in the presence of CL, and the results obtained with family compliance to CL wear and occlusion therapy in the light of existing studies.

Contact lenses in paediatric aphakia in the Netherlands; A multicentre retrospective chart study.

PURPOSE: The main aim of this study was to evaluate the type, parameters, loss and complications of contact lenses (CLs) in the treatment of paediatric aphakia over a 10-year period. METHODS: This retrospective multicentre chart review included the files of aphakic CL wearers under the age of 9 years old that were treated between 2008 and 2018. Patients with traumatic aphakia and scarring of the cornea were excluded. The following data were collected; demographic data, cataract type (congenital or secondary), CL type, parameters and wearing time, reason for replacement and discontinuation of the CLs, visual acuity (VA), prophylactic use of antibiotics (ABs), and complications. RESULTS: Ninety-one aphakic children (132 eyes) were fitted with soft CLs. The median age of cataract extraction was 10.50 weeks (interquartile range (IQR) 7,15) in the congenital cataract group and 112 weeks (IQR 41,285) in the secondary cataract group. At the initial fitting a silicone elastomer CL was fitted in 86 % and a silicone hydrogel CL in 12 %, the remaining 2 % were mixed CL types. The median CL power at baseline was + 29 D (IQR 25,32) and after 3 years of wear the median power had shifted significantly to + 20 D (IQR 17,26), P < 0.001. A total of 1083 extra CL replacements were needed of which 414 in the first year of wear. Of these 414 replacements almost half (46 %;n = 191) were due to loss of the CL. Complications developed in 8 (9 %) cases and 7 (8 %) patients discontinued CL wear. CONCLUSION: This paper confirms that paediatric aphakia can be successfully treated with soft CLs with low rates of complications and discontinuation encountered. Unscheduled CL replacements due to loss are a concern, especially in the first year, and are straining for both the care giver and medical system. Attentive care and clear information is advised during the first year of CL wear.

Case report: Whole exome sequencing identified a novel mutation (p.Y301H) of MAF in a Chinese family with congenital cataracts.

Background: Congenital cataracts stand as the primary cause of childhood blindness globally, characterized by clouding of the eye's lens at birth or shortly thereafter. Previous investigations have unveiled that a variant in the V-MAF avian musculoaponeurotic-fibrosarcoma oncogene homolog (MAF) gene can result in Ayme-Gripp syndrome and solitary cataract. Notably, MAF mutations have been infrequently reported in recent years. Methods: In this investigation, we recruited a Chinese family with non-syndromic cataracts. Whole exome sequencing and Sanger sequencing were applied to scrutinize the genetic anomaly within the family. Results: Through whole exome sequencing and subsequent data filtration, a new mutation (NM_005360, c.901T>C/p.Y301H) in the MAF gene was detected. Sanger sequencing validated the presence of this mutation in another affected individual. The p.Y301H mutation, situated in an evolutionarily preserved locus, was not detected in our 200 local control cohorts and various public databases. Additionally, multiple bioinformatic programs predicted that the mutation was deleterious and disrupted the bindings between MAF and its targets. Conclusion: Hence, we have documented a new MAF mutation within a Chinese family exhibiting isolated congenital cataracts. Our study has the potential to broaden the spectrum of MAF mutations, offering insights into the mechanisms underlying cataract formation and facilitating genetic counseling and early diagnosis for congenital cataract patients.

Ocular Pathology and Genetics: Transformative Role of Artificial Intelligence (AI) in Anterior Segment Diseases.

Artificial intelligence (AI) has become a revolutionary influence in the field of ophthalmology, providing unparalleled capabilities in data analysis and pattern recognition. This narrative review delves into the crucial role that AI plays, particularly in the context of anterior segment diseases with a genetic basis. Corneal dystrophies (CDs) exhibit significant genetic diversity, manifested by irregular substance deposition in the cornea. AI-driven diagnostic tools exhibit promising accuracy in the identification and classification of corneal diseases. Importantly, chat generative pre-trained transformer (ChatGPT)-4.0 shows significant advancement over its predecessor, ChatGPT-3.5. In the realm of glaucoma, AI significantly contributes to precise diagnostics through inventive algorithms and machine learning models, surpassing conventional methods. The incorporation of AI in predicting glaucoma progression and its role in augmenting diagnostic efficiency is readily apparent. Additionally, AI-powered models prove beneficial for early identification and risk assessment in cases of congenital cataracts, characterized by diverse inheritance patterns. Machine learning models achieving exceptional discrimination in identifying congenital cataracts underscore AI's remarkable potential. The review concludes by emphasizing the promising implications of AI in managing anterior segment diseases, spanning from early detection to the tailoring of personalized treatment strategies. These advancements signal a paradigm shift in ophthalmic care, offering optimism for enhanced patient outcomes and more streamlined healthcare delivery.

Characteristic cytokine profile of the aqueous humor in eyes with congenital cataract and pre-existing posterior capsule dysfunction.

Objectives: To investigate the characteristic cytokine profile of the aqueous humor in eyes with congenital cataract and pre-existing posterior capsule dysfunction (PCD). Methods: In this cross-sectional study, the enrolled eyes with congenital cataract and PCD were included in the PCD group, while those with an intact posterior capsule were included in the control group. Demographic data and biometric parameters were recorded. The levels of 17 inflammatory factors in the aqueous humor collected from the enrolled eyes were detected using Luminex xMAP technology, and intergroup differences in the collected data were analyzed. Results: The PCD group comprised 41 eyes from 31 patients with congenital cataract and PCD, whereas the control group comprised 42 eyes from 27 patients with congenital cataract and an intact posterior capsule. Lens thickness was significantly thinner in the PCD group than in the control group. However, the levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-ß2 (TGF-ß2), and vascular endothelial growth factor (VEGF) were significantly higher in the PCD group than in the control group. Multivariate logistic regression confirmed that lens thickness and TGF-ß2 level were independent risk factors for PCD. Conclusion: A thinner lens thickness in eyes with congenital cataract and PCD could serve as a biometric feature of these eyes. The higher levels of MCP-1, TGF-ß2, and VEGF in eyes with PCD indicated a change in their intraocular inflammatory microenvironment, which possibly led to cataract progression. Lens thickness and TGF-ß2 level are independent risk factors for PCD.

Two siblings with PEX11B-related peroxisome biogenesis disorder.

The PEX11ß gene contains four exons and encodes peroxisomal membrane protein 11ß, which is involved in peroxisome proliferation and division. Pathogenic variants in this gene result in a rare genetic disorder with autosomal recessive inheritance called peroxisome biogenesis disorder 14B (MIM: 614920). Here, we report two affected siblings with a novel variant (NM_003846: c.11G > A, p. Trp4Ter) in the PEX11ß gene that was identified by whole exome sequencing and confirmed by Sanger sequencing. The proband is a 22-year-old Iranian female who was born to consanguineous parents. The homozygous variant (NM_003846: c.11G > A, p. Trp4Ter) in the PEX11ß gene was identified in the proband, who presented with cataracts, strabismus, nystagmus, intellectual disability, developmental delay, speech disorders, dry skin, and behavioral problems. Her younger affected brother, who had the same homozygous variant, suffered from similar but slightly milder symptoms. This paper reports the seventh family in the world with novel pathogenic variants in the PEX11ß gene as the cause of peroxisome biogenesis disorder 14B. Additionally, the phenotypes of the previously reported patients are reviewed. Some of the phenotypes, such as bilateral congenital cataracts and intellectual disability, were present in all patients. However, other observed symptoms in previous cases, such as abnormal gait, myopia, abnormal muscle strength, hearing loss, gastrointestinal problems, skeletal disorders, and seizures, were not observed in the patients of this study. Further studies on this disorder could be valuable in determining the precise phenotype characteristics of this disease.

Microphthalmia and congenital cataract in two patients with Stickler syndrome type II: a case report.

BACKGROUND: Stickler syndrome (STL) is a collagenopathy caused by pathogenic variants in collagen-coding genes, mainly COL2A1 or COL11A1 associated with Stickler syndrome type 1 (STL1) or type 2 (STL2), respectively. Affected individuals manifest ocular, auditory, articular, and craniofacial findings in varying degrees. Previous literature and case reports describe high variability in clinical findings for patients with STL. With this case report, we broaden the clinical spectrum of the phenotype. MATERIALS AND METHODS: Case report on two members of a family (mother and son) including clinical examination and genetic testing using targeted trio whole exome sequencing (trio-WES). RESULTS: A boy and his mother presented with microphthalmia, congenital cataract, ptosis, and moderate-to-severe sensorineural hearing loss. Trio-WES found a novel heterozygote missense variant, c.4526A>G; p(Gln1509Arg) in COL11A1 in both affected individuals. CONCLUSIONS: We report a previously undescribed phenotype associated with a COL11A1-variant in a mother and son, expanding the spectrum for phenotype-genotype correlation in STL2, presenting with microphthalmia, congenital cataract, and ptosis not normally associated with Stickler syndrome.

Refractive index adjustable intraocular lens design to achieve diopter control for improving the treatment of ametropia after cataract surgery.

Intraocular lens (IOL) implantation is currently the most effective clinical treatment for cataracts. Nevertheless, due to the growth of the eye axis in patients with congenital cataracts during the process of growth and development, the progressive incapacity of an IOL with a fixed focus does not meet the demands of practical usage, leading to the occurrence of ametropia. This work describes an innovative class of an IOL bulk material that offers good biosafety and light-controlled refractive index adjustment. Acrylate materials were synthesized for the preparation of IOLs by free radical polymerization of ethylene glycol phenyl ether methacrylate (EGPEMA), hydrophilic monomer 2-(2-ethoxyethoxy) ethyl acrylate (EA), and functional monomer hydroxymethyl coumarin methacrylate (CMA). Under 365/254 nm ultraviolet (UV) irradiation, the coumarin group could adjust the polymer material's refractive index through reversible photoinduced dimerization/depolymerization. Meanwhile, the potential for the IOL use is enabled by its satisfactory biosafety. Such a light-induced diopter adjustable IOL will be more appropriate for implantation during cataract surgery since it will not require the correction needed for ametropia and will offer more accurate and humane treatment. STATEMENT OF SIGNIFICANCE.

Long-term risk of glaucoma after cataract surgery in childhood.

PURPOSE: To examine the long-term risk of glaucoma after cataract surgery in childhood. METHODS: This study took place from January 2022 until December 2022 and included patients from a large family with hereditary childhood cataract who had cataract surgery before 18 years of age. Patients underwent an ophthalmologic examination to determine the presence of glaucoma or ocular hypertension (OHT). Patients who did not want to participate in the examination could contribute with a medical journal from their treating ophthalmologist. The risk of long-term glaucoma was determined using survival analysis, and risk factors were assessed using a Cox proportional hazards regression model. RESULTS: We included 68 patients (133 eyes) with a median age at cataract surgery of 7 years (IQR: 5-10). The median follow-up time after cataract surgery to glaucoma/OHT or the latest ophthalmologic examination was 35 years (IQR: 15-48). Twelve patients (18 eyes) had glaucoma, and five patients (eight eyes) had OHT, resulting in 15 patients with glaucoma/OHT. The long-term risk of glaucoma/OHT diagnosed in adulthood was 47.7% (CI: 21.8-70.9) at the age of 70 years of patients who were free of glaucoma before their 18th year. We could not confirm or dismiss an association between glaucoma/OHT and sex, age at surgery, number of ocular interventions before 18 years of age or glaucoma after cataract surgery in a first-degree relative. CONCLUSION: Cataract surgery in childhood is associated with a high risk of late-onset glaucoma. Regular lifelong follow-up is important to ensure early diagnosis and prevent extensive vision loss.

Ocular severe involvement in oculofaciocardiodental syndrome: Description of a case series.

BACKGROUND: Oculofaciocardiodental (OFCD) syndrome is a rare genetic disorder affecting ocular, facial, dental, and cardiac systems, being an X-linked condition caused by pathogenic variants in the BCL-6 corepressor gene (BCOR). We report a case series of three female patients with OFCD syndrome with severe glaucoma. RESULTS: Three female patients with OFCD syndrome with different variants involving BCOR gene, in heterozygosity: a seven-years-old girl with an insertion (c.2037_2038dupCT), a nine years-old girl with a microdeletion in the X (p21.2-p11.4)) spanning the BCOR gene; and a 25 years-old female with a deletion (c.3858_3859del). Systemic involvement is variable among patients ranging from one patient mainly with ocular and dental involvement to one with associated intra-auricular and intra-ventricular defects. All the patients presented with congenital cataracts diagnosed in the first days of life. Cataract surgery was performed without incidents between 6 and 16 weeks of age in all the patients. Postoperatively, the three patients developed ocular hypertension and glaucoma with the need for surgical interventions, including trabeculectomy, Ahmed valve implantation, and cyclophotocoagulation. CONCLUSION: OFCD syndrome characterizes by a severe ocular involvement with glaucoma as a characteristic feature. Ocular hypertension after cataract surgery in these patients is challenging, almost always needing surgery during childhood. Therefore, we consider BCOR disruption may predispose to a higher incidence of glaucoma due to its aggressiveness and early onset on our case series. The awareness of these complications is crucial to an adequate follow-up of the patients.

Seroprevalence of ToRCH Pathogens among Children Admitted to a Tertiary Care Hospital in Eastern India for Cataract Surgery and Cochlear Transplantation.

AIMS: The study aims to investigate the presence of TORCH infections in a child with bilateral cataracts and deafness and report the ToRCH-serology screening profile (Toxoplasma gondii (TOX), rubella (RV), cytomegalovirus (CMV), and herpes simplex virus (HSV-I/II)) in pediatric cataract and deafness. METHODS: Cases that had a clear clinical history of congenital cataracts and congenital deafness were included in the study. The study population consisted of 18 bilateral cataracts and 12 bilateral deafness child who was admitted to AIIMS Bhubaneswar for cataract surgery and cochlear implantation, respectively. Sera of all children were tested qualitatively and quantitatively for IgG/IgM-antibodies against ToRCH agents in a sequential manner. RESULTS: Anti-IgG antibodies against the torch panel were detected in all cataract and deafness patients. Anti-CMV IgG was detected in 17 of 18 bilateral cataract children and 11 of 12 bilateral deaf children. The rates of anti-CMV IgG antibody positivity were significantly higher. In the cataract group, 94.44% and in the deafness group, 91.66% of the patient was Anti-CMV IgG positive. Besides this, 77.7 % of the patient from the cataract group and 75% from the deafness group was anti- RV IgG antibody positive. In bilateral cataract patients, IgG-alone seropositive cases were mostly attributed to CMV (94.44%; 17/18), followed by RV (77.70%; 14/18), HSV-I (27.70%; 5/18), TOX (27.70%; 5/18), and HSV-II (16.60%; 3/18). In bilateral deafness patients, the spectrum of IgG alone seropositive cases was almost the same except for TOX (0/12). CONCLUSION: The current study recommends interpreting ToRCH-screening in pediatric cataracts and deafness with caution. Interpretation should include both serial qualitative and quantitative assays in tandem with clinical correlation to minimize diagnostic errors. The sero-clinical-positivity needs to be tested in older children who might pose a threat to the spread of infection.

Long-term outcomes of intraoperative triamcinolone injection versus postoperative oral prednisolone in congenital cataract surgery / Resultados de longo prazo do uso intraoperatório de triancinolona versus oral pós-operatório de prednisolona na cirurgia de catarata congênita

ABSTRACT Purpose: To compare the long-term ocular findings of children that were operated of congenital cataract before the age of two and that received an intraoperative intracameral triamcinolone injection or used postoperative oral prednisolone to modulate ocular inflammation. Methods: All patients who had previously participated in a clinical trial that analyzed the 1-year surgical outcomes of congenital cataract surgery utilizing intracameral triamcinolone (study group) or oral prednisolone (control group) were eligible to participate in this prospective cohort research. Patients' medical records were reviewed, and the children underwent a complete ophthalmologic exam on final follow-up. Biomicroscopic findings, intraocular pressure, central corneal thickness, the need for additional surgical interventions, and findings compatible with glaucoma were the primary end measures. Results: Twenty-six eyes (26 patients) were included (study group = 11 eyes; control group = 15 eyes). The mean follow--up was 8.2 ± 1.2 years and 8.1 ± 1.7 years in the study and control groups, respectively (p=0.82). All eyes presented a centered intraocular lens. There was no statistically significant difference between the groups with regards to the presence of posterior synechia (p=0.56), intraocular pressure (p=0.49), or central corneal thickness (p=0.21). None of the eyes fulfilled the glaucoma diagnostic criteria, presented secondary visual axis obscuration, or were reoperated. Conclusion: The long--term ocular findings of children that underwent congenital cataract surgery and received an intraoperative intracameral triamcinolone injection were similar to those that used postoperative oral prednisolone to modulate ocular inflammation. This suggests that intracameral triamcinolone may substitute oral prednisolone in congenital cataract surgery, facilitating the postoperative treatment regimen and compliance.

RESUMO Objetivo: Comparar os achados oculares em longo prazo de crianças que se submeteram à cirurgia de catarata congênita antes dos dois anos de idade e receberam uma injeção intracameral de triancinolona no intraoperatório ou usaram prednisolona oral no pós-operatório para modular a inflamação ocular. Métodos: Neste estudo prospectivo de coorte, todos os pacientes que participaram de um ensaio clínico anterior, que analisou os resultados cirúrgicos de 1 ano da cirurgia de catarata congênita usando triancinolona intracameral (Grupo de Estudo) ou prednisolona oral (Grupo Controle), eram elegíveis para participar. Os prontuários médicos dos pacientes foram revisados e as crianças foram submetidas a um exame oftalmológico completo no acompanhamento final. As principais medidas de desfecho foram: achados biomicroscópicos, pressão intraocular, espessura central da córnea, a necessidade de intervenções cirúrgicas adicionais e achados compatíveis com glaucoma. Resultados: Vinte e seis olhos (26 pacientes) foram incluídos (Grupo de Estudo = 11 olhos; Grupo de Controle = 15 olhos). O seguimento médio foi de 8,2 ± 1,2 anos e 8,1 ± 1,7 anos nos Grupos de Estudo e Controle, respectivamente (p=0,82). Todos os olhos apresentavam lente intraocular centrada. Não houve diferença estatisticamente significativa entre os grupos com relação à presença de sinéquia posterior (p=0,56), pressão intraocular (p=0,49) ou espessura central da córnea (p=0,21). Nenhum dos olhos preencheu os critérios diagnósticos para glaucoma, apresentou opacificação secundária do eixo visual ou foi reoperado. Conclusão: Os achados oculares em longo prazo de crianças que se submeteram à cirurgia de catarata congênita e receberam uma injeção intracameral de triancinolona no intraoperatório foram semelhantes aos que usaram prednisolona oral no pós-operatório para modular a inflamação ocular, sugerindo que a triancinolona intracameral pode substituir a prednisolona oral na cirurgia de catarata congênita, facilitando o tratamento pós-operatório e a adesão ao mesmo.

Catarata congênita nas infecções intrauterinas mais comuns (STORCH): revisão de literatura / Congenital cataract in the most common intrauterine infections (STORCH): a review of the literature

RESUMO Objetivo: O objetivo deste estudo foi revisar os aspectos clínicos e patológicos da catarata congênita secundária às infecções por sífilis, toxoplasmose, rubéola, citomegalovírus e herpes simples. Métodos: Trata-se de uma revisão de literatura, na qual foram incluídos artigos de periódicos indexados às bases de dados PubMed®, Cochrane, Lilacs, Embase e SciELO de 2010 a 2023. Resultados: Foram encontrados 45 artigos, e, após seleção, restaram 9 artigos. Além disso, foram adicionados artigos para enriquecer a discussão. A infecção por sífilis está relacionada a alterações corneanas. O citomegalovírus e a toxoplasmose estão relacionados com a coriorretinite e/ou microftalmia. A rubéola é responsável por causar catarata, glaucoma, microftalmia e retinite em sal e pimenta. Conclusão: Foram abordadas as principais etiologias infecciosas e seu quadro clínico na CC. O melhor tratamento para CC é cirúrgico associado a acompanhamento clínico, mas a prevenção é a maneira mais eficaz de combater a CC de etiologia infecciosa. O diagnóstico precoce e o tratamento efetivo previnem alterações e sequelas visuais irreversíveis. Nesse contexto, mostram-se importantes as ações de políticas públicas para o melhor desfecho clínico e melhor qualidade de vida.

ABSTRACT Objective: To review the clinical and pathological aspects of CC secondary to infections by syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes simplex. Methods: This is a literature review. Articles from journals indexed to PubMed, COCHRANE, LILACS, EMBASE and SCIELO from 2010 to 2023 were included. Results: A total of 45 articles were found, which, after selection, remained in 9 articles. Some articles were included to enrich the discussion in this topic. The infection caused by syphilis is related to corneal changes. Cytomegalovirus and Toxoplasmosis due to chorioretinitis and/or microphthalmia. Rubella is responsible for causing cataracts, glaucoma, microphthalmia, and salt and pepper retinitis. Conclusion: The main infectious etiologies and their clinical status in CC were addressed. The best treatment for CC is surgery associated with clinical follow-up, but prevention is the most effective way to combat CC of infectious etiology. Early diagnosis and effective treatment prevent irreversible visual changes and sequelae. In this context, public policy actions are important for the best clinical outcome and better quality of life.

A novel single-base deletional mutation of MIP impairs protein distribution and cell-to-cell adhesion in autosomal dominant cataracts in a Chinese family.

Congenital cataracts are the leading cause of irreversible visual disability in children, and genetic factors play an important role in their development. In this study, targeted exome sequencing revealed a novel single-base deletional mutation of MIP (c.301delG; p.Ala101Profs*16) segregated with congenital punctate cataract in a Chinese family. The hydrophobic properties, and secondary and tertiary structures for truncated MIP were predicted to affect the function of protein by bioinformatics analysis. When MIP-WT and MIP-Ala101fs expression constructs were singly transfected into HeLa cells, it was found that the mRNA level showed no significant difference, while the protein level of the mutant was remarkably reduced compared to that of the wild-type MIP. Immunofluorescence images showed that the MIP-WT was principally localized to the plasma membrane, whereas the MIP-Ala101fs protein was aberrantly trapped in the cytoplasm. Furthermore, the cell-to-cell adhesion capability and the cell-to-cell communication property were both significantly reduced for MIP-Ala101fs compared to the MIP-WT (all *p < 0.05). This is the first report of the c.301delG mutation in the MIP gene associated with autosomal dominant congenital cataracts. We propose that the cataract is caused by the decreased protein expression and reduced cell-to-cell adhesion by the mutant MIP. The impaired trafficking or instability of the mutant protein, as well as compromised intercellular communication is probably a concurrent result of the mutation. The results expand the genetic and phenotypic spectra of MIP and help to better understand the molecular basis of congenital cataracts.

Novel CRYGC Mutation in Conserved Ultraviolet-Protective Tryptophan (p.Trp131Arg) Is Linked to Autosomal Dominant Congenital Cataract.

Congenital cataract (CC), the most prevalent cause of childhood blindness and amblyopia, necessitates prompt and precise genetic diagnosis. The objective of this study is to identify the underlying genetic cause in a Swiss patient with isolated CC. Whole exome sequencing (WES) and copy number variation (CNV) analysis were conducted for variant identification in a patient born with a total binocular CC without a family history of CC. Sanger Sequencing was used to confirm the variant and segregation analysis was used to screen the non-affected parents. The first de novo missense mutation at c.391T>C was identified in exon 3 of CRYGC on chromosome 2 causing the substitution of a highly conserved Tryptophan to an Arginine located at p.Trp131Arg. Previous studies exhibit significant changes in the tertiary structure of the crystallin family in the following variant locus, making CRYGC prone to aggregation aggravated by photodamage resulting in cataract. The variant can be classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria (PP3 + PM1 + PM2 + PS2; scoring 10 points). The identification of this novel variant expands the existing knowledge on the range of variants found in the CRYGC gene and contributes to a better comprehension of cataract heterogeneity.

Cytokines in aqueous humor of patients with congenital cataract during delayed sequential bilateral cataract surgery.

BACKGROUND: To explore the changes of cytokines expression in aqueous humor (AH) of eyes of patients with congenital cataract (CC) who underwent delayed sequential bilateral cataract surgery (DSBCS). METHODS: 28 patients with CC underwent DSBCS. AH samples were collected from each eye before surgery. The contents of cytokines in AH were detected by Luminex xMAP Technology. RESULTS: There was no significant difference in the expression of IL-8, IP-10, MCP-1 and PDGFAA in the AH of the first and second eyes (P = 0.35, 0.39, 0.17, respectively). The level of IL-8 in the first-eye AH was negatively correlated with age (ρ=- 0.519, P = 0.008). IP-10 and MCP-1 in the second-eye AH were negatively correlated with age (ρ=- 0.483, P = 0.009; ρ=- 0.445, P = 0.018,respectively). CONCLUSION: The first-eye surgery in patients with CC may not cause the change of cytokines in the contralateral eye. The expression of IL-8, IP-10 and MCP-1 in the AH was negatively correlated with the age of patients. TRIAL REGISTRATION: The study was registered at www.chictr.org.cn on March 22, 2022 and the clinical trial number is ChiCTR2200057927.