Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts

Congenital cataracts are a major cause of bilateral visual impairment in childhood. We mapped the gene responsible for autosomal congenital cerulean cataracts to chromosome 2q33-35 in a four generation family of Moroccan descent. The maximum lod score (7.19 at recombination fraction theta=0) was obtained for marker D2S2208 near the g-crystallin gene (CRYG) cluster. Sequencing of the coding regions of the CRYGA, B, C, and D genes showed the presence of a heterozygous C>A transversion in exon 2 of CRYGD that is associated with cataracts in this family. This mutation resulted in a proline to threonine substitution at amino acid 23 of the protein in the first of the four Greek key motifs that characterise this protein. We show that although the x ray crystallography modelling does not indicate any change of the backbone conformation, the mutation affects a region of the Greek key motif that is important for determining the topology of this protein fold. Our data suggest strongly that the proline to threonine substitution may alter the protein folding or decrease the thermodynamic stability or solubility of the protein. Furthermore, this is the first report of a mutation in this gene resulting in autosomal dominant congenital cerulean cataracts

Molecular and genetic mechanism of non-syndromic congenital cataracts. Mutation screening in Spanish families

Our purpose was to identify mutations responsible for non-syndromic congenital cataracts through the implementation of next-generation sequencing (NGS) in our center. A sample of peripheral blood was obtained from probands and willing family members and genomic DNA was extracted from leukocytes. DNA was analyzed implementing a panel (OFTv2.1) including 39 known congenital cataracts disease genes. 62 probands from 51 families were recruited. Pathogenic or likely pathogenic variants were identified in 32 patients and 25 families; in 16 families (64%) these were de novo mutations. The mutation detection rate was 49%. Almost all reported mutations were autosomal dominant. Mutations in crystallin genes were found in 30% of the probands. Mutations in membrane proteins were detected in seven families (two in GJA3 and five in GJA8). Mutations in LIM2 and MIP were each found in three families. Other mutations detected affected EPHA2, PAX6, HSF4 and PITX3. Variants classified as of unknown significance were found in 5 families (9.8%), affecting CRYBB3, LIM2, EPHA2, ABCB6 and TDRD7. Mutations lead to different cataract phenotypes within the same familyThis research was funded by ONCE grant number 2020/0197782 and by FIS grant number PI18-1234-ISCII

Catarata pediátrica: aspectos clínicos, frequência de estrabismo e características cronológicas, etiológicas e morfológicas

Objetivos: Avaliar as frequências do estrabismo e as características cronológica, etiológica e morfológica das cataratas pediátricas. Método: Estudo retrospectivo dos prontuários de crianças atendidas no Ambulatório de Catarata Congênita do Departamento de Oftalmologia da Universidade Federal de São Paulo no período entre 2001 e 2011. Foram incluídos pacientes com diagnóstico de catarata congênita ou de desenvolvimento. Foram excluídos os pacientes com catarata traumática; secundárias a uveíte, radiação ou medicamentos; pacientes operados em outro serviço; pacientes com glaucoma; leucocorias não cristalinianas (retinoblastoma, retinopatia da prematuridade, leucocorias pré-cristalinianas), e com sub-luxação do cristalino. Foram avaliadas: as frequências cronológicas, etiológicas e morfológicas das cataratas; a lateralidade e a ocorrência de estrabismo associado nestes pacientes. Resultados: Foram incluídos 207 pacientes. Cento e dezessete (56,5%) apresentavam catarata congênita e 90 (43,5%) apresentavam catarata de desenvolvimento. Cento e nove (52,6%) pacientes eram portadores de catarata unilateral. Quanto à morfologia, 72 crianças (33,8%) apresentavam catarata zonular e 66 (31,9%) apresentavam catarata total. A etiologia idiopática foi a mais frequente (72,5%) afetando 150 pacientes. Foram observados 108 pacientes (52,2%) com estrabismo associado, especialmente endotropias secundárias. Conclusões: A etiologia idiopática foi a mais frequente neste estudo. O tipo morfológico zonular foi o mais frequentemente diagnosticado. Cataratas unilaterais ocorreram mais frequentemente em pacientes com persistência da vasculatura fetal. O estrabismo associado ocorreu em 52% dos pacientes. A análise dos resultados deste estudo pode contribuir para diagnosticar a catarata pediátrica precocemente e de modo mais preciso.Federal University of São Paulo Department of OphthalmologyUniversity of Rio Grande do Sul Hospital de Clínicas de Porto Alegre Department of OphthalmologyUNIFESP, Department of OphthalmologySciEL

Cataract How Important Is Age of Intervention?

Purpose: To study effect of age of intervention on visual outcome following treatment of pediatric patients with cataract. Setting: Tertiary eye care centre in Dahod at the trijunction of Gujarat, Madhya Pradesh, and Rajasthan states in central western India. Participants: 705 eyes of 1047 patients Methods: This is a prospective cohort study. We studied a consecutive series of pediatric patients with congenital, developing, or COMPLICATED cataracts who underwent surgery between January, 1999 and April, 2012 at our center. Patient demographics, cataract type, presenting symptoms, surgical intervention, postoperative visual acuity, and follow-up refractive changes were recorded. Primary Outcome measures: vision. Results: In total, 1305 eyes of 1047 children were included: unilateral cataracts were present in 786 (60.2%) eyes. There were 600 (46.7%) traumatic and 705 (53.3%) non-traumatic cases. Ages at surgery ranged from 1 to 215 months. Eyes were grouped by the age of surgical intervention performed: Group 1,</= 5 years including 177 (25.1%) eyes, and Group 2, >5 years, including 528 (74.9%) eyes either by anterior or pars plana route ± IOL placement. The mean follow-up time was 117 days. Ultimately, 128 (18.2%) Group 1 and 213 (30.2%) Group 2 patients achieved a visual acuity better than 20/80 (P < 0.001). Age at intervention was significantly related (all P < 0.001) to visual outcome. Conclusions: Age of intervention affects visual outcome significantly (p<0.001)

A Comparative study of Increase in Central Corneal Thickness following Congenital Cataract Surgery in Pseudophakic and Aphakic Eyes

INTRODUCTION: A Congenital cataract is defined as any loss of transparency or opacification of the lens fibres present at birth. The incidence rate of paediatric cataracts in developing countries like India is high and 7.4-15.3% of childhood blindness is due to cataract. Although cataract extraction in children is performed at early ages to prevent stimulus deprivation amblyopia, other complications, such as secondary glaucoma, continue to threaten the visual outcome. The thickened cornea after congenital cataract extraction can lead to overestimation of Intra Ocular Pressure (IOP) readings. This can cause over diagnosis of aphakic glaucoma along with overuse of anti-glaucoma medications. Overestimation or underestimation IOP in these patients can have a significant impact on their treatment and overall prognosis. AIMS AND OBJECTIVES: 1. To determine the central corneal thickness in pseudophakics and aphakics following congenital cataract surgery in children. 2. To compare the central corneal thickness in pseudophakics and aphakics following congenital cataract surgery with age matched healthy controls. MATERIALS & METHOD: This is a comparative cross sectional study and the study was conducted among 32 post-operative cases of congenital cataract attending the OPD as well as wards of department of Ophthalmology as well as Institute of Paediatrics in Government Rajaji Hospital Madurai. Subjects are evaluated for entry into the study. Subjects who fulfilled all eligibility criteria, and none of the exclusion criteria, were recruited in our study. METHODOLOGY: 32 cases following congenital cataract surgery, including 19 aphakic eyes and 41 pseudophakic eyes were recruited for the study after obtaining consent from their guardians. Written informed consent was obtained from the parents / guardians of the cases recruited into the study. Visual acuity was recorded in cooperative children. A detailed evaluation of the anterior and posterior segment was carried out. Intra ocular pressure was recorded with the help of Goldmann applanation tonometry in cooperative children and hand held applanation tonometer in uncooperative small children. Central corneal thickness (CCT) measurements were taken with Ultrasonic pachymetry. After explaining the procedure, local anaesthetic drops (0.5% propararcaine) was instilled into the eyes. After 5 minutes, child is reassured and asked to fix at a distant target. CCT is measured by placing the tip of the probe gently on the centre of cornea. An average of 5 readings is taken. Uncooperative children were examined under sedation. RESULTS: A total of 32 post operative cases of congenital cataract were studied, which included 19 aphakic eyes and 41 pseudophakic eyes. The age distribution of cases and controls varied from 4-12 years majority being in the range between 6-8 years of age with a male preponderance. The age at which lensectomy was done in study group varied from 1-5 years, most of them being in the range of 2-3 years. The mean CCT of study group was found to be 583.50 μm ranging from 500-612 μm. The central corneal thickness in aphakic group ranged from 550 μm to 612 μm, mean value being 595.68 μm. The central corneal thickness in pseudophakic group ranged from 490 μm to 588 μm, mean value in primary pseudophakics being 521.42 μm and for secondary pseudophakics it was 554.62 μm. CCT was found to be higher in secondary pseudophakics when compared to their primary counterparts. The IOP values in the study group ranged between 12-32 mm of Hg, the mean IOP being 22.88 mm of Hg. There was a significant difference in CCT between the study group and control group. There was a significant positive correlation (r=0.525) between CCT and IOP in the study group. CONCLUSION: Children who have undergone lens extraction for congenital cataract are found to have a clinically significant increase in central corneal thickness which can in turn provide overestimated intraocular pressure readings by applanation tonometry. Aphakic eyes have a thicker cornea when compared to their pseudophakic counterpart showing primary lens implantation can be a protective factor against this increase. So measuring central corneal thickness should be made mandatory and necessary intra ocular pressure corrections made before prescribing antiglaucoma medications in children who are highly susceptible to their serious side effects

Últimos retos en el tratamiento de la catarata congénita

La descripció de la cataracta congènita és una opacitat de la lent ocular que apareix en el part o durant la primera infància, és una malaltia rara i sovint desconeguda, però a excepció d'altres raons associades amb ella que inclouen: genètica, metabòlica, infeccions, ús de corticoesteroides, trauma, uveitis, així com anomalies oculars. L'objectiu d'aquest treball és investigar diversos articles sobre els últims reptes del tractament de la cataracta congènita i quins tipus d'enfocaments es poden utilitzar per curar-los i per a l'ambliopia que es produeix a causa de la cataracta. Per a concloure, malgrat l'avanç de les tècniques quirúrgiques per als nens molt millor del que ho va ser fa anys, així que els reptes com la mida de l'ull, l'edat, la selecció d'exàmens de l'OL, l'horari de cirurgia i les complicacions, així com la remodelació de la visió post-cirúrgica; encara existeixen, però sobretot la rehabilitació de la visió i el tractament amblòpic per a les condicions post-cirúrgiques, i per a aquests casos menors, han de ser seguits periòdicament.La descripción de la catarata congénita es una opacidad del cristalino que aparece en el parto o durante la primera infancia, es una enfermedad rara y muchas veces de causa desconocida, pero salvo por otras razones asociadas a ella que incluyen; genéticas, metabólicas, infecciones, uso de corticoides, traumatismos, uveítis, así como anomalías oculares. El objetivo de este trabajo es investigar varios artículos sobre los últimos desafíos del tratamiento de la catarata congénita y qué tipos de enfoques se pueden utilizar para curarlos y para la ambliopía que se produce debido a la catarata. Para concluir, a pesar del avance en las técnicas quirúrgicas para niños mucho mejor que hace años, los desafíos como el tamaño del ojo, la edad, la selección de exámenes de LIO, el cronograma de cirugía y las complicaciones, así como la rehabilitación de la visión posquirúrgica; aún existen, pero sobre todo la rehabilitación de la visión y el tratamiento ambliópico para condiciones post-quirúrgicas, y para aquellos casos menores, deben ser objeto de un seguimiento periódico.The description of congenital cataract is an opaqueness of eye lens that appears at childbirth or during early childhood, It is a rare disease and often unknown cause, but except for other reasons associated with it that include; genetic, metabolic, infections, corticosteroids usage, trauma, uveitis, as well as ocular anomalies. The goal of this work is to research various articles on the latest challenges of treating congenital cataract and what kinds of approaches can be used for curing them and for the amblyopia that is produced due to cataract. To conclude, in spite of the advancement in surgical techniques for children much better than it was years ago, so the challenges such as eye size, age, selection of IOL examinations, surgery schedule, and complications, as well as vision rehab post-surgical; still exist, but most of all the vision rehabilitation and amblyopic treatment for post-surgical conditions, and for those minor cases, they must be followed up periodically

A novel 1-bp deletion in PITX3 causing congenital posterior polar cataract

Purpose: Cataracts are the most common cause of blindness worldwide. Inherited cataract is a clinically and genetically heterogeneous disease. Here we report a novel mutation in the paired-like homeodomain 3 (PITX3) gene segregating in a four generation English family with an isolated autosomal dominant posterior polar cataract.Methods: A genome-wide linkage was performed by means of single nucleotide polymorphism (SNP) and microsatellite markers. Linkage analyses were performed with the GeneHunter and MLINK programs. Direct sequencing of PCR products was performed to detect mutation in the gene, using the BigDye version 3.1 and analyzed using Sequence analysis version 5.2.Results: Genome-wide linkage analysis with SNP markers, identified a disease-haplotype interval on chromosome 10q. Two point positive logarithm of odds (LOD) scores was obtained with markers D10S205 (Z=3.10 at theta=0.00), flanked by markers D10S1709 and D10S543, which harbors the homeobox gene PITX3. Sequence analysis of PITX3 revealed a 1-bp deletion that cosegregated with all the affected members of this family which resulted in a frameshift in codon 181 and likely to produce an aberrant protein consisting of 127 additional residues.Conclusions: The 542delC is a novel mutation in PITX3 causing an isolated posterior polar cataract