Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.856
Filtrar
1.
Yi Chuan ; 42(2): 161-171, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32102773

RESUMO

Congenital cataract (CC) is a rare disease with dysplasia of the lens, mainly characterized by partial or complete opacity of the lens. The molecular basis of the disease is complex, mutations in over 266 genes associated with congenital cataracts had been reported. In this study, a novel congenital cataract candidate gene TSR1 was identified by whole genome sequencing and Sanger sequencing in a Chinese congenital cataract family. The TSR1 c.202-1G>A substitution affected splicing of TSR1 mRNA was confirmed by a minigene assay. The expression of TSR1 in mouse lens, anterior lens capsule of age-related cataract patients and 24-week human fetal lens were determined by RT-PCR, Western blotting, and immunofluorescence assays. The expression of TSR1 in the embryonic and different developmental stages of the mouse lens was confirmed by analyzing the iSyTE database. The expression of TSR1 was down-regulated in the lens-specific CBP:p300 double knockout mouse, and a set of genes with the same expression pattern of Tsr1 in the CBP:p300 double knockout mouse lens were extracted for protein-protein interaction network analysis, and six proteins were screened for direct interaction with Tsr1. GO function analysis indicated that Tsr1 might play a role in the MAPK-Erk signaling pathway in addition to its involvement in ribosome assembly. This study provided valuable research clues to further clarify the function of Tsr1 in the lens.


Assuntos
Catarata/genética , Cristalino/patologia , Proteínas Ribossômicas/genética , Animais , Grupo com Ancestrais do Continente Asiático , Catarata/congênito , China , Humanos , Camundongos , Camundongos Knockout , Mutação , Linhagem , RNA Mensageiro
2.
BMC Med Genet ; 20(1): 196, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842807

RESUMO

BACKGROUND: Congenital cataract is a clinically and genetically heterogeneous visual impairment. The aim of this study was to identify causative mutations in five unrelated Chinese families diagnosed with congenital cataracts. METHODS: Detailed family history and clinical data were collected, and ophthalmological examinations were performed using slit-lamp photography. Genomic DNA was extracted from peripheral blood of all available members. Thirty-eight genes associated with cataract were captured and sequenced in 5 typical nonsyndromic congenital cataract probands by targeted next-generation sequencing (NGS), and the results were confirmed by Sanger sequencing. Bioinformatics analysis was performed to predict the functional effect of mutant genes. RESULTS: Results from the DNA sequencing revealed five potential causative mutations: c.154 T > C(p.F52 L) in GJA8 of Family 1, c.1152_1153insG(p.S385Efs*83) in GJA3 of Family 2, c.1804 G > C(p.G602R) in BFSP1 of Family 3, c.1532C > T(p.T511 M) in EPHA2 of Family 4 and c.356G > A(p.R119H) in HSF4 of Family 5. These mutations co-segregated with all affected individuals in the families and were not found in unaffected family members nor in 50 controls. Bioinformatics analysis from several prediction tools supported the possible pathogenicity of these mutations. CONCLUSIONS: In this study, we identified five novel mutations (c.154 T > C in GJA8, c.1152_1153insG in GJA3, c.1804G > C in BFSP1, c.1532C > T in EPHA2, c.356G > A in HSF4) in five Chinese families with hereditary cataracts, respectively. NGS can be used as an effective tool for molecular diagnosis of genetically heterogeneous disorders such as congenital cataract, and the results can provide more effective clinical diagnosis and genetic counseling for the five families.


Assuntos
Catarata/congênito , Catarata/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Catarata/fisiopatologia , China , Biologia Computacional , Feminino , Humanos , Masculino , Linhagem , Facoemulsificação , Acuidade Visual
3.
Invest Ophthalmol Vis Sci ; 60(14): 4717-4726, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31725171

RESUMO

Purpose: To identify the genetic defect in a four-generation Chinese family that causes autosomal dominant congenital posterior subcapsular cataracts, and to understand how this EPHA2 kinase domain mutation affects EPHA2 activity. Methods: Variants in 54 cataract-associated genes were screened by targeted next generation sequencing (NGS) and then validated by Sanger sequencing. EPHA2 wild-type cDNA was synthesized in vitro, and EPHA2 p.G668D mutant was constructed by PCR site-directed mutagenesis. Western blotting and fluorescence microscopy were used to analyze the expression level of protein and its subcellular localization, respectively. A wound-healing assay was performed to analyze changes to cell migration. Results: A novel heterozygous missense mutation was identified in the kinase domain of the EPHA2 gene (c.2003G>A, p.G668D). This is the third congenital cataract mutation being reported in this domain. Functional study revealed that the kinase domain mutation (p.G668D) decreased EphA2 protein level (P = 0.036) via a proteasome-dependent pathway, altered its subcellular localization of the EphA2 from cell-cell contacts to a diffuse perimembranous distribution, and changed the distribution of ß-catenin as well. The expression of mutant EphA2 significantly promoted the migration of human lens epithelial cells (P = 0.002). Conclusions: Our study presented the evidence for a novel EPHA2 kinase domain mutation that causes congenital posterior subcapsular cataracts. The first functional study on an EPHA2 kinase domain mutation that causes a congenital cataract revealed that the G668D mutation destabilized the receptor, changed its subcellular localization, and altered the activation of EphA2 with its ligand ephrin. The mutant EphA2 resulted in a reduced inhibition of cell migration. As a consequence, the c.G668D mutation promoted cell migration and caused the formation of cataracts.


Assuntos
Catarata/congênito , Catarata/genética , Efrina-A2/metabolismo , Mutação de Sentido Incorreto , Receptor EphA2/genética , Grupo com Ancestrais do Continente Asiático/genética , Western Blotting , Catarata/enzimologia , Catarata/patologia , Movimento Celular/fisiologia , Células Cultivadas , China/epidemiologia , Análise Mutacional de DNA , Células Epiteliais/metabolismo , Feminino , Vetores Genéticos , Células HEK293 , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Lentivirus/genética , Masculino , Microscopia de Fluorescência , Mutagênese Sítio-Dirigida , Linhagem , Plasmídeos , Reação em Cadeia da Polimerase , Receptor EphA2/metabolismo , beta Catenina/metabolismo
4.
Invest Ophthalmol Vis Sci ; 60(13): 4388-4396, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634396

RESUMO

Purpose: To explore the impact of childhood lensectomy on posterior segment development. Methods: Cross-sectional observational study at children's eye clinics at a tertiary referral center in London, UK. We included 45 children age 4 to 16 years with healthy eyes and 38 who had undergone lensectomy. We acquired posterior segment optical coherence tomography scans of both eyes. We used parametric and nonparametric tests in SPSS24 for the comparison of parameters between groups and within individuals; a P value less than 0.05 was considered significant. The main outcome measures were foveal pit depth and subfoveal choroidal thickness (CT). Secondary outcomes were inner and outer ring CT and photoreceptor layer parameters, macular and peripapillary retinal nerve fiber layer thickness. Results: Foveal pit depth and subfoveal CT are significantly reduced in eyes that have undergone lensectomy compared with nonoperated eyes. Inner ring CT and outer ring CT are reduced. Foveal inner retinal layer thickness is increased. Mean inner retinal and outer nuclear layer thickness are not affected. Conclusions: Childhood lensectomy is associated with a reduction in developmental foveal pit deepening and lack of developmental thickening of the posterior choroid. Mechanical and optical disruption of foveal and subfoveal choroidal development may affect structural foveal development after childhood lensectomy.


Assuntos
Extração de Catarata , Catarata/congênito , Corioide/crescimento & desenvolvimento , Fóvea Central/crescimento & desenvolvimento , Segmento Posterior do Olho/crescimento & desenvolvimento , Adolescente , Criança , Pré-Escolar , Corioide/diagnóstico por imagem , Corioide/patologia , Estudos Transversais , Feminino , Fóvea Central/diagnóstico por imagem , Fóvea Central/patologia , Humanos , Masculino , Fibras Nervosas/patologia , Células Fotorreceptoras de Vertebrados/patologia , Segmento Posterior do Olho/diagnóstico por imagem , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual/fisiologia
5.
Medicine (Baltimore) ; 98(39): e17342, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574874

RESUMO

RATIONALE: The karyotype 49,XXXXY is a rare form of Klinefelter syndrome usually presenting with ambiguous genitalia, facial dysmorphism, mental retardation, and a combination of cardiac, skeletal, and other malformations. PATIENT CONCERNS: We describe a 19-year-old man, whose chromosomal analysis of peripheral blood revealed a karyotype of 49,XXXXY. His mental development and motor ability were significantly delayed. At the age of 19, he had failed to develop secondary sexual characteristics. His random blood glucose level was 19.61 mmol/L, and he showed dry mouth, polydipsia, and polyuria. He had a characteristic facial appearance with prognathism, widened nasal bridge, and strabismus. His bilateral elbow rotation was limited. He had atrophic testes with micropenis. Ophthalmic examination revealed a polar cataract in both eyes. DIAGNOSIS: He was diagnosed with Klinefelter syndrome associated with cleft palate, hypothyroidism, cataracts, diabetes, and other anomalies. INTERVENTIONS: After the initial diagnosis, the patient received intensive insulin therapy to correct hyperglycemia, and he received calcium and vitamin D supplements. The patient also received testosterone and thyroid hormone replacement therapy for primary hypogonadism. OUTCOMES: The patient was discharged 12 days after receiving treatment; meanwhile, there were no clinical symptoms of dry mouth, polyuria and polyuria, and his blood glucose level was controlled. LESSONS: The combination of cleft palate, hypothyroidism, cataracts, diabetes, and osteoporosis in 49,XXXXY syndrome has not yet been reported. Early treatment and appropriate care can significantly improve the patient's quality of life and prevent serious consequences.


Assuntos
Catarata/congênito , Fissura Palatina/genética , Hipotireoidismo Congênito/genética , Diabetes Mellitus/congênito , Transtornos dos Cromossomos Sexuais/complicações , Anormalidades Múltiplas/genética , Aneuploidia , Cromossomos Humanos X/genética , Humanos , Cariotipagem , Masculino , Aberrações dos Cromossomos Sexuais , Transtornos dos Cromossomos Sexuais/genética , Adulto Jovem
6.
BMC Med Genet ; 20(1): 153, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488069

RESUMO

BACKGROUND: Mutations in more than 52 genes have been identified in isolated congenital cataracts, the majority of which are located in crystalline and connexin (gap junction) genes. An in-frame one amino acid deletion in the beta-crystalline gene CRYBA1 has been reported in several different Chinese, Caucasian and Iranian families of congenital cataracts. Further functional studies are needed to confirm the variant pathogenicity. METHODS: The purpose of this study is to identify the genetic causes that contribute to congenital cataracts with esotropia and nystagmus in a Chinese family. Whole-exome sequencing was performed on samples from all five family members. The two brothers of the father and their daughters were then enrolled in the study, and 40 suspected variants were sequenced among the 9 subjects using Sanger sequencing. The mRNA and protein levels of CRYBA1 in the lens epithelium from cataract patients and normal controls were compared using quantitative polymerase chain reaction (qPCR) and Western blot analyses. The wild-type and mutated forms (p.G91del) of CRYBA1 cDNA were transfected into two types of cell lines, and the expression level of exogenous CRYBA1 was measured by Western blot analysis. The exogenous CRYBA1 proteins were visualized by immunofluorescence staining. RESULTS: In this two-generation family, all three descendants inherited congenital cataracts with esotropia and nystagmus from the father, while the mother's lens was normal. After two rounds of sequencing, CRYBA1 (c. 269-271 del, p.G91del) was identified as the mutation responsible for the autosomal dominant congenital cataract in the Chinese family. CRYBA1 showed lower expression in cataract lenses than in control lenses. The deleted form (p.G91del) of CRYBA1 showed lower expression and was more aggregate to the cell membrane than the wild-type CRYBA1. CONCLUSIONS: We performed molecular experiments to confirm that the p.G91del mutation in CRYBA1 results in abnormal expression and distribution of CRYBA1 protein, and this study could serve as an example of the pathogenicity of an in-frame small deletion in an inherited eye disorder.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Catarata/congênito , Catarata/genética , Predisposição Genética para Doença/genética , Deleção de Sequência , Cadeia A de beta-Cristalina/genética , Idoso , Sequência de Bases , Catarata/diagnóstico por imagem , Catarata/patologia , Linhagem Celular , Grupo com Ancestrais do Continente Europeu , Feminino , Regulação da Expressão Gênica , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Sequenciamento Completo do Exoma , Cadeia A de beta-Cristalina/metabolismo
8.
Arch. Soc. Esp. Oftalmol ; 94(8): 377-383, ago. 2019. graf
Artigo em Espanhol | IBECS | ID: ibc-185623

RESUMO

Objetivo: Estudiar la presión intraocular postoperatoria (PIOP) elevada tras la intervención de catarata pediátrica en un centro de referencia y comparar los resultados obtenidos con aquellos más relevantes de la literatura mundial. Materiales y métodos: Estudio retrospectivo observacional. Recogida de información de historias clínicas de 99 pacientes (142 ojos) operados de catarata pediátrica unilateral o bilateral entre los años 2000 y 2008. Resultados: La frecuencia de PIOP elevada (≥ 20 mmHg) fue de 79,3% en el grupo de catarata bilateral frente al 20,7% en el grupo de catarata unilateral (p = 0,032). La frecuencia de PIOP elevada entre los ojos con cirugía de catarata antes del mes de edad fue mayor, 50%, que entre los ojos en los que la cirugía de catarata se realizó después del mes de edad, 17,2% (p = 0,009). Los valores de PIOP ≥ 20mmHg se asociaron con una menor agudeza visual mejor corregida a los 5 años de la cirugía de catarata (p = 0,020). La proporción de ojos con PIOP ≥ 20 mmHg y sin lentes intraoculares fue mayor, 69%, que la proporción de ojos con PIOP ≥ 20 mmHg y lentes intraoculares, 31% (p < 0,001). Conclusiones: Un 20,4% del total de ojos estudiados presentaron PIOP elevada ≥ 20 mmHg en un periodo de seguimiento de 5 años, apareciendo con más frecuencia en aquellos con catarata bilateral que unilateral, y en ojos afáquicos que en pseudofáquicos. La elevación de la PIOP se asoció con la realización de la cirugía de la catarata a edades tempranas


Objective: To study elevated postoperative intraocular pressure (PIOP) after paediatric cataract surgery in a reference centre and to compare the results obtained with the most relevant world literature. Materials and methods: A retrospective observational study was conducted, collecting information from clinical records of 99 patients (142 eyes) operated on due to unilateral or bilateral paediatric cataracts between 2000 and 2008. Results: The proportion of eyes with PIOP ≥ 20 mmHg and bilateral cataracts was higher, 79.3%, than the proportion of eyes with PIOP ≥ 20mmHg and a unilateral cataract, 20.7% (P = .032). The proportion of eyes with PIOP ≥ 20 mmHg between the eyes with cataract surgery before one month of age was higher, 50%, than between the eyes in which the cataract surgery was performed after one month of age, 17.2% (P=.009). PIOP values ≥ 20 mmHg were associated with a lower best corrected visual acuity at 5 years after cataract surgery (P = .020). The proportion of eyes with PIOP ≥ 20 mmHg and without intraocular lenses was higher, 69%, than the proportion of eyes with PIOP ≥ 20 mmHg and intraocular lenses, 31% (P < .001). Conclusions: A PIOP > 20 mmHg was observed in 20.4% of eyes in a 5-year follow-up period, appearing more frequently in eyes with bilateral cataract than unilateral, and in aphakic eyes more than pseudophakic eyes. Elevation of the PIOP was associated with the performance of cataract surgery at early ages


Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Catarata/congênito , Extração de Catarata/efeitos adversos , Hipertensão Ocular/etiologia , Complicações Pós-Operatórias/etiologia , Fatores Etários , Catarata/patologia , Extração de Catarata/métodos , Extração de Catarata/estatística & dados numéricos , Pressão Intraocular , Implante de Lente Intraocular , Microftalmia/complicações , Hipertensão Ocular/diagnóstico , Estudos Retrospectivos , Acuidade Visual
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(7): 697-700, 2019 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-31302914

RESUMO

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with congenital cataracts. METHODS: Clinical data and peripheral blood samples were collected for the pedigree. Following extraction of genomic DNA, whole exome sequencing was carried out to detect genetic variants. Candidate variants were verified by familial co-segregation analysis and Sanger sequencing. Bioinformatics analysis was carried out to predict the function of mutant genes. RESULTS: By comparing variants identified among affected and unaffected individuals, a heterozygous variant, c.110 G>C (p.R37P), was identified in exon 2 of the CRYGC gene among all patients, which also matched the criteria for potential disease-causing mutations. The result was confirmed by Sanger sequencing. CONCLUSION: The c.110G>C variant of the CRYGC gene probably underlay the congenital cataracts in this pedigree.


Assuntos
Catarata/congênito , Catarata/genética , gama-Cristalinas/genética , Grupo com Ancestrais do Continente Asiático , China , Heterozigoto , Humanos , Mutação , Linhagem
10.
Arch Soc Esp Oftalmol ; 94(8): 377-383, 2019 Aug.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31221471

RESUMO

OBJECTIVE: To study elevated postoperative intraocular pressure (PIOP) after paediatric cataract surgery in a reference centre and to compare the results obtained with the most relevant world literature. MATERIALS AND METHODS: A retrospective observational study was conducted, collecting information from clinical records of 99 patients (142 eyes) operated on due to unilateral or bilateral paediatric cataracts between 2000 and 2008. RESULTS: The proportion of eyes with PIOP≥20mmHg and bilateral cataracts was higher, 79.3%, than the proportion of eyes with PIOP≥20mmHg and a unilateral cataract, 20.7% (P=.032). The proportion of eyes with PIOP≥20mmHg between the eyes with cataract surgery before one month of age was higher, 50%, than between the eyes in which the cataract surgery was performed after one month of age, 17.2% (P=.009). PIOP values≥20mmHg were associated with a lower best corrected visual acuity at 5 years after cataract surgery (P=.020). The proportion of eyes with PIOP≥20mmHg and without intraocular lenses was higher, 69%, than the proportion of eyes with PIOP≥20mmHg and intraocular lenses, 31% (P<.001). CONCLUSIONS: A PIOP>20mmHg was observed in 20.4% of eyes in a 5-year follow-up period, appearing more frequently in eyes with bilateral cataract than unilateral, and in aphakic eyes more than pseudophakic eyes. Elevation of the PIOP was associated with the performance of cataract surgery at early ages.


Assuntos
Extração de Catarata/efeitos adversos , Catarata/congênito , Hipertensão Ocular/etiologia , Complicações Pós-Operatórias/etiologia , Fatores Etários , Catarata/patologia , Extração de Catarata/métodos , Extração de Catarata/estatística & dados numéricos , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Pressão Intraocular , Implante de Lente Intraocular , Microftalmia/complicações , Hipertensão Ocular/diagnóstico , Estudos Retrospectivos , Acuidade Visual
11.
Exp Eye Res ; 186: 107712, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31254514

RESUMO

Crystallins are structural proteins in the lens that last a lifetime with little turnover. Deviant in crystallins can cause rare but severe visual impairment, namely, congenital cataracts. It is reported that several mutations in the acidic ß-crystallin 4 (CRYBA4) are related to congenital cataracts. However, the pathogenesis of these mutants is not well understood at molecular level. Here we evaluate the biochemical properties of wild type CRYBA4 (CRYBA4WT) and a pathogenic G64W mutant (CRYBA4G64W) including protein folding, polymerization state and protein stability. Furthermore, we explore the differences in their interactions with α-crystallin A (CRYAA) and basic ß-crystallin 1 (CRYBB1) via yeast two-hybrid and pull-down assay in vitro, through which we find that G64W mutation leads to protein misfolding, decreases protein stability, blocks its interaction with CRYBB1 but maintains its interaction with CRYAA. Our results deepen our understanding of the pathogenesis of congenital cataracts.


Assuntos
Catarata , Cristalino/metabolismo , Dobramento de Proteína , Cadeia A de beta-Cristalina/genética , beta-Cristalinas/química , Catarata/congênito , Catarata/genética , Catarata/metabolismo , Humanos , Mutação
12.
Mol Med Rep ; 20(1): 559-566, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180551

RESUMO

It is well known that transforming growth factor ß (TGFß), which is able to stimulate multiple intracellular signaling pathways, exerts an important role in Marfan syndrome, although the effects of TGFß on congenital ectopia lentis (CEL) have yet to be fully elucidated. In the present study, the expression levels of TGFß and matrix metalloproteinases (MMPs) were investigated in the aqueous humor of patients with ectopic lentis who differed in terms of the severity of the disease. A total of 17 CEL patients with 21 eyes (aged 12.76±9.37 years) and 12 congenital cataract (CC) patients with 17 eyes (aged 6.82±9.18 years) were randomized in the present study. The levels of active TGFß and MMPs in the aqueous humor were analyzed with Luminex xMAP® technology by using commercially available Bio­Plex Pro™ Human MMP and TGFß assays. The distance from the lens edge to the pupil edge and the white to white corneal diameter (i.e. the horizontal distance between the borders of the corneal limbus) were measured, and the ratio was calculated as the degree of lens dislocation. The association between TGFß and MMP levels and the degree of lens dislocation was analyzed using Spearman's correlation test. Compared with the patients with CC, the level of TGFß2 in the patients with CEL was increased significantly. Specifically, the level of TGFß2 in the CEL patients was 855.19 pg/ml (744.33, 1,009.24), whereas it was 557.08 (438.24, 692.71) pg/ml in the CC patients (P<0.001). In addition, it was noted that the levels of MMP­2 and ­10 in the aqueous humor of the patients with CEL were higher compared with those in the CC patients, although this increase did not reach the level of statistical significance. Notably, the levels of MMP­8 and ­9 in the aqueous humor of patients with CEL were significantly lower compared with those in the CC patients (P=0.014 and P=0.002, respectively). Furthermore, a marginal correlation was identified between the severity of ectopic lentis and the levels of TGFß2 in the aqueous humor (r2=0.379; P=0.003) of the patients with CEL. Taken together, these results demonstrated that a significant correlation existed between high levels of aqueous humor TGFß2 and the severity of ectopia lentis in patients with CEL. In addition, aqueous humor TGFß2 levels in the CEL patients were significantly higher compared with those in CC patients.


Assuntos
Humor Aquoso/química , Ectopia do Cristalino/patologia , Metaloproteinases da Matriz/análise , Fator de Crescimento Transformador beta2/análise , Adolescente , Adulto , Catarata/congênito , Catarata/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Fator de Crescimento Transformador beta/análise , Adulto Jovem
14.
Indian J Ophthalmol ; 67(6): 785-787, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31124487

RESUMO

Purpose: To study the clinicopathological findings of Persistent Fetal Vasculature (PFV) in patients with congenital cataract and PFV. Methods: Six eyes with anterior or combined PFV with cataract underwent phacoaspiration with primary posterior capsulotomy with anterior vitrectomy with intraocular lens implantation followed by histopathological evaluation of the PFV stalk and membrane. Results: Four and two patients had combined and anterior PFV respectively. There was no postoperative hyphema, vitreous haemorrhage, glaucoma or retinal detachment in six months. Haematoxylin and eosin staining showed inflammatory cells predominantly with extramedullary hematopoeisis and vascularisation. Conclusion: We recommend IOL implantation in PFV, with early and aggressive amblyopia therapy.


Assuntos
Vítreo Primário Hiperplásico Persistente/diagnóstico , Vitrectomia/métodos , Corpo Vítreo/patologia , Catarata/congênito , Seguimentos , Humanos , Lactente , Recém-Nascido , Lentes Intraoculares , Masculino , Microscopia Acústica , Vítreo Primário Hiperplásico Persistente/terapia , Facoemulsificação , Prognóstico , Estudos Prospectivos , Corpo Vítreo/cirurgia
15.
Cornea ; 38(8): 1003-1005, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31045961

RESUMO

PURPOSE: We explored elevated central corneal thickness (CCT) in children with cataracts as possibly reflecting preexisting corneal malformation related to specific cataract morphology. METHODS: All children consecutively seen during the study periods who had cataracts and corneal pachymetry as part of their routine care were enrolled at academic centers in large cities of Canada and the United States. Study data collected included age, sex, CCT, and cataract morphology. Differences among cataract morphology groups with respect to mean CCT measurements were evaluated and compared with a historical control thickness of 558 µm. RESULTS: A total of 96 children were enrolled in this study. The average subject age was 5.1 years, and 55 children (57%) were female. The mean CCT value for all subjects was 566.1 µm. There was little evidence to conclude that the cataract morphology groups differed from each other (P = 0.65) or from controls with respect to CCT. CONCLUSIONS: In children, CCT is likely independent of cataract morphology. This implies that factors other than preoperative malformation are more likely related to elevated CCT observed in children with aphakia and pseudophakia.


Assuntos
Catarata/congênito , Córnea/patologia , Adolescente , Estudos de Casos e Controles , Extração de Catarata , Criança , Pré-Escolar , Paquimetria Corneana , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Tamanho do Órgão , Estudos Prospectivos , Estudos Retrospectivos
17.
FEBS Open Bio ; 9(5): 840-850, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31034164

RESUMO

Connexins (Cx) are proteins that form cell-to-cell gap junction channels. A mutation at position 188 in the second extracellular loop (E2) domain of hCx46 has been linked to an autosomal dominant zonular pulverulent cataract. As it is dominantly inherited, it is possible that the mutant variant affects the co-expressed wild-type Cx and/or its interaction with other cellular components. Here, we proposed to use concatenated hCx46wt-hCx46N188T and hCx46N188T-hCx46wt to analyze how hCx46N188T affected co-expressed hCx46wt to achieve a dominant inheritance. Heterodimer hCx46wt-hCx46N188T formed fewer gap junction plaques compared to homodimer hCx46wt-hCx46wt, while the hCx46N188T-hCx46N188T homodimer formed almost no gap junction plaques. Dye uptake experiments showed that hemichannels of concatenated variants were similar to hemichannels of monomers. Molecular dynamics simulations revealed that for docking, the N188 of a protomer was engaged in hydrogen bonds (HBs) with R180, N189, and D191 of the counterpart protomer of the adjacent hemichannel. T188 suppressed the formation of HBs between protomers. Molecular dynamics simulations of an equimolar hCx46wt/hCx46N188T gap junction channel revealed a reduced number of HBs between protomers, suggesting reduction of gap junction channels between lens fibers co-expressing the variants.


Assuntos
Conexinas/genética , DNA Concatenado/genética , Simulação de Dinâmica Molecular , Mutação/genética , Catarata/congênito , Catarata/genética , Conexinas/metabolismo , DNA Concatenado/metabolismo , Junções Comunicantes/genética , Células HeLa , Humanos
18.
Mol Med Rep ; 19(5): 4419-4424, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30942463

RESUMO

Nance­Horan syndrome (NHS) is a rare X­linked disorder with various clinical manifestations. The present study aimed to identify the pathogenic mutation causing NHS in a three­generation Chinese family with 4 individuals presenting primarily with congenital cataracts. The genomic DNA of 5 individuals was collected, and family history and clinical information were recorded. Whole exome sequencing was performed on the proband, and candidate mutations were filtered by a series of screening processes and validated by Sanger sequencing. The identified pathogenic mutation was confirmed by co­segregation analysis. Finally, a novel frameshift mutation (NM_001291867.1: c.302dupA; p.Ala102fs) was identified in the NHS actin remodeling regulator (NHS) gene, which co­segregated with congenital cataracts in this family. Carrier females exhibited similar but milder clinical symptoms compared with the affected male. These clinical symptoms were consistent with the phenotypic features of the NHS­associated disease, NHS. In summary, the present study identified a novel NHS mutation in a Chinese family with atypical NHS; the results broaden the known pathogenic mutation spectrum of NHS and will aid in the genetic counseling of patients with NHS. The data from the present study also suggest that genetic analysis may be required for the diagnosis of this disease.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Catarata/congênito , Doenças Genéticas Ligadas ao Cromossomo X/genética , Proteínas Nucleares/genética , Anormalidades Dentárias/genética , Adulto , Catarata/genética , Catarata/patologia , Pré-Escolar , Feminino , Mutação da Fase de Leitura , Genes Ligados ao Cromossomo X , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Humanos , Masculino , Linhagem , Anormalidades Dentárias/patologia , Sequenciamento Completo do Exoma
19.
PLoS One ; 14(4): e0214684, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30933995

RESUMO

OBJECTIVE: This meta-analysis aims to evaluate the incidence of secondary glaucoma in patients under the age of 2 years who underwent congenital cataract surgery with or without primary intraocular lens (IOL) implantation. METHODS: An electronic literature search was performed in Medline, EMBASE, and Web of Science databases to retrieve studies between January 2011 and November 2018. Patients with congenital cataract who did primary IOL implantation, aphakia, or secondary IOL implantation followed by receiving extraction surgery were included in this study. Relevant studies meeting defined eligibility criteria were selected and reviewed systematically by meta-analysis. Long-term incidences of secondary glaucoma, which developed at least one year after cataract surgery, were considered and discussed as clinical outcomes in each cohort. The pooled data were analyzed according to a random effects model. RESULTS: Eight publications involving 892 eyes were included in the current meta-analysis. In the general population of eyes with congenital cataract, the long-term incidence of secondary glaucoma was lower (P = 0.06) in eyes with primary IOL (9.5%) than in eyes without primary IOL (15.1%), including aphakia and secondary IOL. The pooled risk ratio (RR) favors primary IOL implantation in all patients (RR = 0.63). For bilateral congenital cataract, the incidence was 6.7% in eyes with primary IOL implantation, which is significantly lower than the 16.7% in eyes with aphakia and secondary IOL implantation (P<0.05, RR = 0.44). However, for unilateral congenital cataract surgery, the incidence was very similar in eyes with and without primary IOL (12.4% vs 12.0%, P = 0.61, RR = 0.87). CONCLUSIONS: In patients under 2 years of age, primary IOL implantation for bilateral congenital cataract surgery is associated with a lower risk of secondary glaucoma.


Assuntos
Afacia Pós-Catarata/cirurgia , Extração de Catarata/efeitos adversos , Catarata/congênito , Glaucoma/etiologia , Glaucoma/prevenção & controle , Implante de Lente Intraocular , Afacia Pós-Catarata/epidemiologia , Opacificação da Cápsula/epidemiologia , Opacificação da Cápsula/etiologia , Opacificação da Cápsula/prevenção & controle , Catarata/epidemiologia , Extração de Catarata/estatística & dados numéricos , Glaucoma/epidemiologia , Humanos , Lactente , Recém-Nascido , Lentes Intraoculares/efeitos adversos , Lentes Intraoculares/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Fatores de Risco
20.
Artigo em Inglês | MEDLINE | ID: mdl-30875852

RESUMO

(1) Background: Oculo-facio-cardio-dental (OFCD) syndrome is a rare pathological condition with an X-linked dominant trait that only occurs in females; no males are born with OFCD syndrome. This syndrome is characterized by congenital cataracts with secondary glaucoma ocular defects, ventricular and atrial septal defects, or mitral valve prolapses. Facial traits are a long narrow face and a high nasal bridge with a bifid nasal tip. Dental anomalies include radiculomegaly, oligodontia, root dilacerations, malocclusion, and delayed eruption. (2) Methods: This clinical report describes a 26-year-old girl who suffers from OFCD syndrome and who was treated with a multidisciplinary approach. The treatment plan included orthodontic treatment, orthognathic surgery, namely LeFort I and a Bilateral Sagittal Split Osteotomy, and occlusal rehabilitation with implants. (3) Discussion: Early diagnosis and multidisciplinary treatment of orthodontic, orthognathic surgery and occlusal rehabilitation with implants make it possible to maintain tooth function and improve aesthetics with good prognoses for success. In this paper, we report a case of a female patient with OFCD syndrome, who was referred for orthodontic treatment and occlusal rehabilitation and treated with a multidisciplinary approach.


Assuntos
Catarata/congênito , Defeitos dos Septos Cardíacos/terapia , Má Oclusão/terapia , Microftalmia/terapia , Procedimentos Cirúrgicos Ortognáticos , Adulto , Catarata/terapia , Feminino , Defeitos dos Septos Cardíacos/cirurgia , Humanos , Má Oclusão/cirurgia , Microftalmia/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA