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Human Genetics Sep 2019Mouse mutants are a long-lasting, valuable tool to identify genes underlying eye diseases, because the absence of eyes, very small eyes and severely affected,... (Review)
Review
Mouse mutants are a long-lasting, valuable tool to identify genes underlying eye diseases, because the absence of eyes, very small eyes and severely affected, cataractous eyes are easily to detect without major technical equipment. In mice, actually 145 genes or loci are known for anophthalmia, 269 for microphthalmia, and 180 for cataracts. Approximately, 25% of the loci are not yet characterized; however, some of the ancient lines are extinct and not available for future research. The phenotypes of the mutants represent a continuous spectrum either in anophthalmia and microphthalmia, or in microphthalmia and cataracts. On the other side, mouse models are still missing for some genes, which have been identified in human families to be causative for anophthalmia, microphthalmia, or cataracts. Finally, the mouse offers the possibility to genetically test the roles of modifiers and the role of SNPs; these aspects open new avenues for ophthalmogenetics in the mouse.
Topics: Animals; Anophthalmos; Cataract; Eye; Humans; Mice; Microphthalmos; Mutation; Phenotype
PubMed: 30919050
DOI: 10.1007/s00439-019-01995-w -
Molecular Genetics and Metabolism Dec 2011Anophthalmia and microphthalmia (A/M) are significant eye defects because they can have profound effects on visual acuity. A/M is associated with non-ocular... (Review)
Review
Anophthalmia and microphthalmia (A/M) are significant eye defects because they can have profound effects on visual acuity. A/M is associated with non-ocular abnormalities in an estimated 33-95% of cases and around 25% of patients have an underlying genetic syndrome that is diagnosable. Syndrome recognition is important for targeted molecular genetic testing, prognosis and for counseling regarding recurrence risks. This review provides clinical and molecular information for several of the commonest syndromes associated with A/M: Anophthalmia-Esophageal-Genital syndrome, caused by SOX2 mutations, Anophthalmia and pituitary abnormalities caused by OTX2 mutations, Matthew-Wood syndrome caused by STRA6 mutations, oculofaciocardiodental syndrome and Lenz microphthalmia caused by BCOR mutations, Microphthalmia Linear Skin pigmentation syndrome caused by HCCS mutations, Anophthalmia, pituitary abnormalities, polysyndactyly caused by BMP4 mutations and Waardenburg anophthalmia caused by mutations in SMOC1. In addition, we briefly discuss the ocular and extraocular phenotypes associated with several other important eye developmental genes, including GDF6, VSX2, RAX, SHH, SIX6 and PAX6.
Topics: Abnormalities, Multiple; Animals; Anophthalmos; Eye; Genes, Developmental; Genetic Association Studies; Humans; Microphthalmos; Mutation; Phenotype; Syndrome
PubMed: 22005280
DOI: 10.1016/j.ymgme.2011.09.029 -
Biology Open Jun 2023As a member of the fibronectin leucine-rich transmembrane (flrt) gene family, fibronectin leucine-rich transmembrane 2 (flrt2) is strongly expressed in a subset of...
As a member of the fibronectin leucine-rich transmembrane (flrt) gene family, fibronectin leucine-rich transmembrane 2 (flrt2) is strongly expressed in a subset of sclerotome cells, and the resultant protein interacts with FGFR1 in the FGF signaling pathway during development. Studies on flrt2 have focused mainly on its roles in the brain, heart and chondrogenesis. However, reports on its expression and function in the zebrafish retina are lacking. Here, we detected the high expression of flrt2 in zebrafish retina using in situ hybridization technique and developed an flrt2-knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. Quantitative real-time PCR was used to measure the expression levels of flrt2, which results in an approximately 60% mRNA reduction. The flrt2-KO zebrafish eyes' altered morphological, cellular, and molecular events were identified using BrdU labeling, TUNEL assay, immunofluorescent staining, fluorescent dye injection and RNA sequencing. Abnormal eye development, known as microphthalmia, was found in flrt2-KO larvae, and the retinal progenitor cells exhibited increased apoptosis, perhaps owing to the combined effects of crx, neurod4, atoh7, and pcdh8 downregulation and Casp3a and Caspbl upregulation. In contrast, the retinal neural development, as well as retinal progenitor cell differentiation and proliferation, were not affected by the flrt2 deletion. Thus, flrt2 appears to play important roles in retinal development and function, which may provide the basis for further investigations into the molecular mechanisms of retinal development and evolution.
Topics: Animals; Fibronectins; Leucine; Membrane Glycoproteins; Microphthalmos; Zebrafish
PubMed: 37259881
DOI: 10.1242/bio.059784 -
Acta Ophthalmologica Dec 2020Congenital anophthalmia (A) and microphthalmia (M) are rare developmental defects, which could be isolated or syndromic. Our objective was to describe a cohort of...
PURPOSE
Congenital anophthalmia (A) and microphthalmia (M) are rare developmental defects, which could be isolated or syndromic. Our objective was to describe a cohort of children and young adults with A/M treated with ocular prosthesis, emphasizing clinical features, diagnosis, treatment, and follow-up.
METHODS
Eighteen individuals (10 female) with unilateral A (n = 3) and M (n = 15) with a mean age of 9.5 years (range 0.8-31.8) and treated with ocular prosthesis were included. Data on medical history, clinical examinations and management of ocular prosthesis were collected. Genetic screening with microarray and whole-exome sequencing targeting 121 A/M-related genes was performed.
RESULTS
A/M appeared isolated (seven cases) or as part of a syndromic condition (11 cases). In 4/16 patients, mutations were detected in TFAP2A, CHD7, FOXE3 and BCOR-genes. In one patient, a possibly causal microdeletion 10q11 was shown. Associated ocular anomalies such as cataract and cysts were found in 16 (89%) of the A/M eyes, and in nine (50%) ophthalmological findings were found in the fellow eyes. The median ages at which the conformer and ocular prosthesis first were initiated were 7.8 months and 1.5 years. 16/17 patients fulfilled satisfactory orbital growth and cosmetic results when treated with ocular prosthesis from an early age.
CONCLUSION
Based upon our findings, a multidisciplinary approach, including genetic assessment, is necessary to cover all aspects of A/M. Imaging, ultrasound and visual evoked potentials should be included. Early management is crucial for the outcome, in terms of non-ocular findings, vision in the fellow eye, and for facial cosmetic development.
Topics: Adolescent; Adult; Anophthalmos; Child; Child, Preschool; Disease Management; Female; Humans; Infant; Male; Microphthalmos; Phenotype; Prognosis; Young Adult
PubMed: 32436650
DOI: 10.1111/aos.14427 -
Scientific Reports Mar 2022Microphthalmia is a rare ocular anomaly with a poorly understood etiology that is most likely related to heritable and/or environmental factors. Many papers have been... (Observational Study)
Observational Study
Microphthalmia is a rare ocular anomaly with a poorly understood etiology that is most likely related to heritable and/or environmental factors. Many papers have been published pertaining to the clinical manifestations and management of this condition; however, few reports have reported detailed histopathological findings, which are the focus of this study, in addition to highlighting the basic demographics in these cases. This was a retrospective, observational study of all consecutive enucleated microphthalmic globes (with or without cysts) at 2 tertiary eye hospitals in Riyadh, Saudi Arabia. Globes were classified into 2 groups: severe microphthalmos (axial length or mean diameter less than 10 mm in infancy or 12 mm after age 1 year) and mild microphthalmos based on larger measurements. Clinical and demographic data collected included sex, age at enucleation, eye involvement, nationality/region, consanguinity, family history of eye anomaly, pregnancy, systemic disease, or syndromes. For histopathological data, a descriptive analysis was mostly performed. For correlations of some of our qualitative data, Fisher's exact test was used. Eleven cases (6 mild and 5 severe microphthalmos) were initially identified with a female to male ratio of 4:7. Ten patients were Saudis, 7 of whom were from the central region. Consanguinity was found in 36% (4/11), and 3 of them had other ocular or systemic abnormalities (duodenal atresia, microcephaly, kidney agenesis, cryptophthalmos, and dysmorphic facial features). Histopathological data were available for 10 cases, half of which showed a coloboma and/or anterior segment anomaly. There was no significant correlation among gender, severity of microphthalmos or the presence of coloboma, although severe microphthalmic globes had a higher median of abnormal intraocular structures (9-interquartile range = 2 compared to 6-interquartile range = 1 in the mild group). Aphakia was found in half of the globes with associated anterior segment dysgenesis. We have concluded that microphthalmos is a visually disabling congenital anomaly that can be isolated or associated with other periocular or systemic anomalies, possibly in relation to consanguinity in our cases. Congenital aphakia was found in half of these cases and was mostly associated with absent Descemet's membrane and agenesis of anterior chamber angle structures, supporting previously suggested embryological concepts. These findings necessitate further wider genetic testing and proper premarital counseling in Saudi Arabia.
Topics: Coloboma; Demography; Eye Abnormalities; Female; Humans; Infant; Male; Microphthalmos; Retrospective Studies
PubMed: 35347187
DOI: 10.1038/s41598-022-09261-2 -
Der Ophthalmologe : Zeitschrift Der... Jan 2022Relative anterior microphthalmos, nanophthalmos and high-grade hyperopia are small eyes with different characteristic morphological relationships between the anterior... (Review)
Review
Relative anterior microphthalmos, nanophthalmos and high-grade hyperopia are small eyes with different characteristic morphological relationships between the anterior segment and axis length. This article discusses the intraoperative challenges and surgical approaches to solutions for cataract operations in patients with one of the three named morphological alterations. Additionally, the article addresses possible comorbidities including glaucoma and preoperative planning.
Topics: Cataract; Humans; Hyperopia; Lens Implantation, Intraocular; Microphthalmos; Phacoemulsification
PubMed: 34453190
DOI: 10.1007/s00347-021-01483-5 -
Romanian Journal of Ophthalmology 2016Abstract
UNLABELLED
Abstract
PURPOSE
We present the clinical, paraclinical and therapeutic features in a patient with secondary congenital aphakia.
METHODS
A 2-year-old patient, diagnosed with congenital rubella syndrome including sensorineural deafness, congenital heart disease, intellectual disability, microcephaly, microphthalmia, and congenital cataract, presented to our clinic for the surgical treatment of cataract.
RESULTS
During the surgery, the absence of the lens' cortex was observed, hence, the final diagnose was of secondary congenital aphakia. Surgery was then continued with a posterior capsulorhexis and an anterior vitrectomy, deciding to postpone the implantation of the posterior chamber intraocular lens.
Topics: Aphakia; Capsulorhexis; Cataract; Child, Preschool; Hearing Loss, Sensorineural; Heart Defects, Congenital; Humans; Intellectual Disability; Male; Microcephaly; Microphthalmos; Rubella Syndrome, Congenital; Treatment Outcome; Vitrectomy
PubMed: 27220231
DOI: No ID Found -
Systematic Reviews Feb 2022Microphthalmos and nanophthalmos are uncommon ocular conditions, whereby affected eyes have smaller dimensions compared to the normal population. Microphthalmos and...
INTRODUCTION
Microphthalmos and nanophthalmos are uncommon ocular conditions, whereby affected eyes have smaller dimensions compared to the normal population. Microphthalmos and nanophthalmos present several challenges to ophthalmologists; they have spontaneous and post-operative sequelae such as high hyperopia, angle-closure glaucoma, uveal effusion syndrome, and retinal detachment. This systematic review and meta-analysis intends to assess the prevalence of both the spontaneous complications associated with nanophthalmos and microphthalmos, as well as the post-surgical complications associated with nanophthalmos or microphthalmos.
METHODS AND ANALYSIS
Articles will be searched for, on four online databases: PubMed, EMBASE, Scopus, and Web of Science. Two independent reviewers will identify the studies according to prespecified inclusion and exclusion criteria. All studies included with participants diagnosed with microphthalmos or nanophthalmos in one or both eyes, will be included if they have (i) more than 4 cases and (ii) defined microphthalmos/nanophthalmos as an axial length of < 21 mm or a high lens/eye volume ratio. Nanophthalmos may have an additional diagnostic criterion of posterior wall thickness greater than 1.7 mm. The prevalence of the following complications will be assessed: high hyperopia (spherical equivalent >3D), angle closure glaucoma, uveal effusion syndrome, retinal detachment, and chorioretinal folds. Studies that will be excluded are those that have not adequately defined the criteria for the diagnosis of nanophthalmos or microphthalmos, those studies that have less than five cases, studies with criteria not defined above, and deemed unsuitable, and studies in languages other than English with no published translation. Relevant data will be extracted and assessed for the risk of bias in each article using a modified Joanna Briggs Institute (JBI) assessment tool. The data will then be pooled to determine the prevalence of complications among patients with microphthalmos and nanophthalmos. If the data allows, subgroup analysis will be carried out according to axial length as well as subtype of microphthalmos/nanophthalmos (simple, complex, relative anterior, and posterior).
DISCUSSION
Although nanophthalmos is an uncommon condition that affects the eye, its management and complications can be sight-threatening. Thus, it is important to counsel patients and their families correctly (in the case of children) upon diagnosis and prior to any surgical intervention. This can only be done if the overall prevalence of complications is known.
REGISTRATION
PROSPERO CRD42021227847.
Topics: Child; Humans; Hyperopia; Meta-Analysis as Topic; Microphthalmos; Prevalence; Systematic Reviews as Topic
PubMed: 35139896
DOI: 10.1186/s13643-022-01889-5 -
Pigment Cell & Melanoma Research Dec 2010The history of the discovery of the microphthalmia locus and its gene, now called Mitf, is a testament to the triumph of serendipity. Although the first microphthalmia... (Review)
Review
The history of the discovery of the microphthalmia locus and its gene, now called Mitf, is a testament to the triumph of serendipity. Although the first microphthalmia mutation was discovered among the descendants of a mouse that was irradiated for the purpose of mutagenesis, the mutation most likely was not radiation induced but occurred spontaneously in one of the parents of a later breeding. Although Mitf might eventually have been identified by other molecular genetic techniques, it was first cloned from a chance transgene insertion at the microphthalmia locus. And although Mitf was found to encode a member of a well-known transcription factor family, its analysis might still be in its infancy had Mitf not turned out to be of crucial importance for the physiology and pathology of many distinct organs, including eye, ear, immune system, bone, and skin, and in particular for melanoma. In fact, near seven decades of Mitf research have led to many insights about development, function, degeneration, and malignancies of a number of specific cell types, and it is hoped that these insights will one day lead to therapies benefitting those afflicted with diseases originating in these cell types.
Topics: Animals; Cloning, Molecular; Genetic Loci; History, 20th Century; Humans; Microphthalmia-Associated Transcription Factor; Microphthalmos
PubMed: 20807369
DOI: 10.1111/j.1755-148X.2010.00759.x -
Gaceta Medica de Mexico 2017Congenital eye malformations are the second most common cause of childhood blindness and are originated by disruption of the normal process of eye development during... (Review)
Review
Congenital eye malformations are the second most common cause of childhood blindness and are originated by disruption of the normal process of eye development during embryonic stage. Their etiology is variable, although monogenic causes are of great importance as they have a high risk of familial recurrence. Included among the most severe congenital eye abnormalities are microphthalmia, defined by an abnormally small eye, and anophthalmia, characterized by congenital absence of ocular structures. The currrent knowledge of the genes involved in human microphthalmia and anophthalmia in humans is revised in this work.
Topics: Anophthalmos; Child; Eye Abnormalities; Gene Expression Regulation, Developmental; Humans; Microphthalmos
PubMed: 29414965
DOI: 10.24875/GMM.17002604