BACKGROUND: The oculo-facio-cardio-dental syndrome (OFCD) is an ultra-rare multiple congenital anomaly. This report describes clinical findings emphasising dental phenotype in five, molecularly confirmed, female cases from two Czech families. CASE PRESENTATION: Dental examinations were carried out. An orthopantomogram was taken in three patients, and all patients' intraoral cavities and teeth were photographed. Exome sequencing was performed in both probands. Results were validated by Sanger DNA sequencing which was also used to follow segregation of the variants in first-degree relatives. Dental abnormalities and congenital cataracts were present in all five cases, whilst other signs were variable and included facial dysmorphism, microphthalmia, and cardiac and skeletal abnormalities. Two individuals had cleft lip and/or cleft palate. Radiculomegaly occurred in three patients with permanent teeth and was diagnosed on orthopantomograms. Two patients had agenesis of permanent teeth. Malocclusion was also present in two patients due to crowding and a Class III malocclusion and mandibular overjet. De novo novel pathogenic variants in the BCOR gene were identified; c.2382del p.(Lys795Argfs*12) and c.3914dup p.(Gln1306Alafs*20) and co-segregated with the disease in each family. CONCLUSIONS: The OFCD syndrome has a unique dental phenotype and dentists should be aware of signs of this ultra-rare genetic disorder. All patients with congenital cataracts and dental abnormalities, including those without a family history, should be referred for genetic testing and indicated to specialised dental care.

• MeSH
• Eye Abnormalities genetics   MeSH
• Tooth Abnormalities * genetics   MeSH
• Heart Septal Defects MeSH
• Child MeSH
• Adult MeSH
• Phenotype MeSH
• Genetic Diseases, X-Linked MeSH
• Cataract genetics   congenital   MeSH
• Humans MeSH
• Microphthalmos * genetics   MeSH
• Adolescent MeSH
• Abnormalities, Multiple genetics   MeSH
• Proto-Oncogene Proteins * genetics   MeSH
• Radiography, Panoramic MeSH
• Repressor Proteins * genetics   MeSH
• Pedigree MeSH
• Heart Defects, Congenital genetics   complications   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Geographicals
• Czech Republic MeSH

• MeSH
• Eye Abnormalities etiology   pathology   therapy   MeSH
• Anophthalmos * etiology   pathology   therapy   MeSH
• Humans MeSH
• Microphthalmos * etiology   pathology   therapy   MeSH
• Infant, Newborn MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Publication type
• Review MeSH

BACKGROUND: Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome. RESULTS: Query of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation. CONCLUSIONS: Using genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease.

• MeSH
• Eye Abnormalities * genetics   MeSH
• Anophthalmos * genetics   MeSH
• Embryonic Development genetics   MeSH
• Phenotype MeSH
• Coloboma * genetics   MeSH
• Humans MeSH
• Microphthalmos * genetics   MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Eye MeSH
• Mammals MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• Eye Abnormalities * diagnosis   etiology   classification   pathology   MeSH
• Anophthalmos diagnosis   etiology   classification   pathology   MeSH
• Diagnosis, Differential MeSH
• Child MeSH
• Encephalocele diagnosis   etiology   classification   pathology   MeSH
• Coloboma diagnosis   classification   pathology   MeSH
• Humans MeSH
• Microphthalmos diagnosis   etiology   classification   pathology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Review MeSH

The Wnt/β-catenin signaling pathway controls many processes during development, including cell proliferation, cell differentiation and tissue homeostasis, and its aberrant regulation has been linked to various pathologies. In this study we investigated the effect of ectopic activation of Wnt/β-catenin signaling during lens fiber cell differentiation. To activate Wnt/β-catenin signaling in lens fiber cells, the transgenic mouse referred to as αA-CLEF was generated, in which the transactivation domain of β-catenin was fused to the DNA-binding protein LEF1, and expression of the transgene was controlled by αA-crystallin promoter. Constitutive activation of Wnt/β-catenin signaling in lens fiber cells of αA-CLEF mice resulted in abnormal and delayed fiber cell differentiation. Moreover, adult αA-CLEF mice developed cataract, microphthalmia and manifested downregulated levels of γ-crystallins in lenses. We provide evidence of aberrant expression of cell cycle regulators in embryonic lenses of αA-CLEF transgenic mice resulting in the delay in cell cycle exit and in the shift of fiber cell differentiation to the central fiber cell compartment. Our results indicate that precise regulation of the Wnt/β-catenin signaling activity during later stages of lens development is essential for proper lens fiber cell differentiation and lens transparency.

• MeSH
• beta Catenin genetics   metabolism   MeSH
• Cell Differentiation genetics   MeSH
• Cell Cycle genetics   MeSH
• DNA-Binding Proteins genetics   metabolism   MeSH
• Epithelial Cells metabolism   MeSH
• Cataract genetics   metabolism   MeSH
• Crystallins genetics   metabolism   MeSH
• Humans MeSH
• Microphthalmos genetics   metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Transgenic genetics   metabolism   MeSH
• Mice MeSH
• Lens, Crystalline metabolism   MeSH
• Promoter Regions, Genetic genetics   MeSH
• Wnt Signaling Pathway genetics   MeSH
• Signal Transduction genetics   MeSH
• Lymphoid Enhancer-Binding Factor 1 MeSH
• Gene Expression Regulation, Developmental MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Aplázia zrakového nervu je veľmi zriedkavou vrodenou chybou oka, ktorá môže byť spojená s ďalšími očnými alebo systémovými ochoreniami. Autori v kazuistike demonštrujú 2,5-mesačné dievčatko s jednostrannou mikroftalmiou, anirídiou a apláziou zrakového nervu.

Optic nerve aplasia is a very rare ocular congenital defect and is invariably associated with other ocular or systemic disorders. The authors demonstrate a case report in the 2.5 month old girl with unilateral mikroftalmia, aniridia and aplasia of the optic nerve.

• MeSH
• Aniridia diagnosis   pathology   MeSH
• Diagnostic Techniques, Ophthalmological MeSH
• Infant MeSH
• Humans MeSH
• Microphthalmos diagnosis   pathology   MeSH
• Optic Nerve Diseases diagnosis   radiography   congenital   MeSH
• Optic Nerve abnormalities   pathology   radiography   MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Publication type
• Case Reports MeSH

PURPOSE: To determine the central corneal thickness (CCT) in microphthalmic aphakic or pseudophakic eyes as well as in microphthalmic eyes without any history of eye surgery. METHODS: Thirty-two patients with a mean age of 6.41±5.24 years after congenital cataract surgery with absolute microcornea, i.e., horizontal corneal diameter (HCD)<10 mm, or relative microcornea, i.e., HCD 10-11 mm but in the affected eye at least 0.5 mm smaller compared to the fellow eye, formed group A. Thirteen patients of mean age 0.94±1.22 years with absolute or relative microcornea plus another developmental anomaly of an eye without any history of eye surgery formed group B. The patients with corneal edema or scars were excluded. The control group consisted of 124 healthy school-aged children. Horizontal corneal diameter was measured with caliper and CCT with an ultrasound pachymeter. In infants, these measurements were performed under general anesthesia. RESULTS: In 48 eyes in group A and in 16 eyes in group B, the mean CCT was 635.13±65.35 µm and 642.31±93.07 µm, respectively, which was significantly greater (p<0.0001 and p=0.0018) in comparison with the mean CCT (553.58±33.12 µm) in the control group. Regression curve demonstrated the significant increase of CCT values along with the decrease of HCD in microphthalmic eyes. CONCLUSIONS: Small corneas in microphthalmic eyes either with or without congenital cataract surgery have significantly higher CCT. The results demonstrate significant negative correlation between horizontal corneal diameter and CCT.

• MeSH
• Aphakia, Postcataract pathology   MeSH
• Diagnostic Techniques, Ophthalmological MeSH
• Child MeSH
• Cataract Extraction MeSH
• Cataract congenital   MeSH
• Infant MeSH
• Humans MeSH
• Microphthalmos pathology   MeSH
• Child, Preschool MeSH
• Pseudophakia pathology   MeSH
• Cornea abnormalities   pathology   MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Esthetics MeSH
• Contact Lenses utilization   MeSH
• Humans MeSH
• Microphthalmos therapy   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Meeting Abstract MeSH
• Case Reports MeSH

PURPOSE: We isolated an autosomal semi-dominant cataract from our inbred SHR/OlaIpcv rat colony. Heterozygotes express pulverulent cataract with smaller eyes; homozygotes express marked microphthalmia with hypoplastic lens. We call this mutation Dca (for dominant cataract). In this study, we focus on the identification of the responsible gene.

• MeSH
• Point Mutation genetics   MeSH
• Phenotype MeSH
• Financing, Organized MeSH
• Glutamine genetics   MeSH
• Cataract genetics   pathology   MeSH
• Connexins genetics   chemistry   MeSH
• Rats MeSH
• Lysine genetics   MeSH
• Chromosome Mapping MeSH
• Microphthalmos genetics   pathology   MeSH
• Molecular Sequence Data MeSH
• Lens, Crystalline pathology   MeSH
• Eye Proteins genetics   chemistry   MeSH
• Amino Acid Sequence MeSH
• Amino Acid Substitution MeSH
• Inheritance Patterns genetics   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH

We propose to use multiple independent molecular approaches to elucidate the importance of the transcription factor MITF in the pathogenesis of human melanoma and the role of transcription factor HASH1 in small cell lung carcinoma. The quantitative estimation of MITF can also be helpful for the diagnosis of melanoma and HASH1 may help in prognostic consideration in small cell lung carcinoma.

Je navrženo několika nezávislými molekulárními přístupy studovat úlohu transkripčního faktoru MITF v patogenezi maligního melanomu a úlohu faktoru HASH1 v patogenezi malobuněčného karcinomu plic. Kvantitativní určení hladiny MITF u melanomu může pomoci při diagnoze a určení hladiny HASH1 při prognóze malobuněčného karcinomu plic.

• MeSH
• Apoptosis MeSH
• Thyroiditis, Autoimmune MeSH
• Carcinoma, Small Cell diagnosis   genetics   pathology   MeSH
• Melanoma, Experimental genetics   MeSH
• Microphthalmos genetics   MeSH
• Transcription Factors MeSH

• Conspectus
• Biochemie. Molekulární biologie. Biofyzika
• NML Fields
• hematologie a transfuzní lékařství
• onkologie
• pneumologie a ftizeologie
• biologie
• NML Publication type
• závěrečné zprávy o řešení grantu IGA MZ ČR