OBJECTIVETo investigate the clinical characteristics and the corneal morphological abnormalities in Fleck corneal dystrophy.

METHODSEighteen eyes with Fleck corneal dystrophy of 9 patients from two unrelated families were examined by slit-lamp biomicroscopy, Cochet-Bonnet esthesiometer and in vivo confocal microscopy. The corneal cells, nerves and stromal deposits were analyzed quantitatively with NAVIS software.

RESULTSlit-lamp biomicroscopy of the Fleck corneal dystrophy revealed that bilateral small grey-white fleck-like or wreath-like opacities were scattered in all layer of the corneal stroma from the center to the periphery, the intervening stroma between the lesions was clear. In vivo confocal microscopy identified that the opacities appeared as doughnut-like or nephroid-like deposits approximately 70.6 μm × 110.3 μm in size, (1.6 ± 0.4)/frame in density and involved about (438.4 ± 22.0) μm of the corneal stroma, with hyper reflective dot-like intracellular particles,measuring 2 to 18 μm in diameter. In two eyes of 1 patient associated with decreased corneal sensation, confocal images showed that abnormal hyper reflective deposits involved the Bowman's layer and the branch and density of the subbasal nerve was reduced. The other eyes with normal corneal sensation appeared normal in the morphology and the density of the corneal nerves.

CONCLUSIONFleck corneal dystrophy has typical clinical characteristics. In vivo confocal microscopy allows to study the morphological changes of the cornea at cellular level, which is valuable for the clinical diagnosis and evaluation of the corneal dystrophy. Decreased corneal sensitivity in Fleck corneal dystrophy is probably caused by corneal stromal deposits involved in the Bowman's layer.

Adolescent ; Adult ; Aged ; Cornea ; pathology ; Corneal Dystrophies, Hereditary ; pathology ; Female ; Humans ; Male ; Microscopy, Confocal ; Middle Aged ; Young Adult

OBJECTIVE: The CYP4V2 gene of two pedigrees affected with Bietti crystalline corneoretinal dystrophy was analyzed to indentify the cause of the disease and provide a basis for clinical diagnosis. METHODS: The probands were subjected to next generation sequencing (NGS). Suspected variants were verified by Sanger sequencing. Pathogenicity of the variants were searched through relevant databases and PubMed by following the ACMG guidelines. RESULTS: A homozygous variant in the CYP4V2 gene c. (802-8) _810delTCATACAGGTCATCGCTinsGC was detected in proband from pedigree 1, parents did not detect; CYP4V2 genes c. (802-8)_810delTCATACAGGTCATCGCTinsGC and c. 958 C>T (p.Arg320X) compound heterozygous variants existed in the proband of pedigree 2,both parents were variant carriers. The results of Sanger sequencing showed that the variant of CYP4V2 gene in the two families was consistent with the NGS sequencing. The c. (802-8)_810delTCATACAGGTCATCGCTinsGC of CYP4V2 gene was splicing variant, and both splicing variant and nonsense variant could produce truncated nonfunctional protein products. Based on standards and guidelines by American College of Medical Genetics and Genomics, the CYP4V2 genes c. (802-8)_810del TCATACAGGTCATCGCTinsGC and c. 958 C>T (p.Arg320X) were predicted to be pathogenic variants (PVS1+PS1+PM2+PM3). CONCLUSION The homozygous variant c. (802-8) _810delTCATACAGGTCATCGCTinsGC and the complex heterozygous variants c. (802-8) _810delTCATACAGGTCATCGCTinsGC and c.958C>T (p.Arg320X) in CYP4V2 gene are the cause of the disease in the probands of two pedigrees , respectively.
Corneal Dystrophies, Hereditary/pathology* ; Cytochrome P450 Family 4/genetics* ; Genetic Variation ; Humans ; Mutation ; Pedigree ; Phenotype ; Retinal Diseases/pathology*

OBJECTIVETo screen the transforming growth factor, beta-induced (TGFBI) gene mutation in three Chinese families with autosomal dominant corneal dystrophy.

METHODSAnalysis of the TGFBI gene mutations was performed by direct sequencing of the whole coding regions and exon-intron boundaries of the TGFBI gene in all affected members from the three families.

RESULTSThree kinds of TGFBI gene mutations, R124C and H626R were detected in the patients of the two lattice conneal dystrophy families, and R124H was detected in the Avellino corneal dystrophy family.

CONCLUSIONTGFBI gene mutations are the underlying molecular mechanism of the pathogenesis for corneal dystrophy. The R124 and H626 are the hot spots of TGFBI gene mutation in this disease.

Asian Continental Ancestry Group ; genetics ; Corneal Dystrophies, Hereditary ; genetics ; pathology ; Corneal Stroma ; pathology ; DNA Mutational Analysis ; Family Health ; Female ; Humans ; Male ; Mutation ; Pedigree ; Transforming Growth Factors ; genetics

BACKGROUNDCorneal dystrophy is a group of inherited blinding diseases of the cornea. This study was to identify the mutations of the keratoepithelin (KE) gene for proper diagnosis of corneal dystrophy.

METHODSThree families with corneal dystrophy were analysed. Thirteen individuals at risk for corneal dystrophy in family A, the proband and her son in family B, and the proband in family C were examined after their blood samples were obtained. Mutation screening of human transforming growth factor beta-induced gene (BIGH3 gene) was performed.

RESULTSFive individuals in family A were found by clinical evaluation to be affected with granular corneal dystrophy and carried the BIGH3 mutation W555R. However, both probands in families B and C, also diagnosed with granular corneal dystrophy, harboured the BIGH3 mutation R124H.

CONCLUSIONMolecular genetic analysis can improve accurate diagnosis of corneal dystrophy.

Adolescent ; Adult ; Child ; Child, Preschool ; Corneal Dystrophies, Hereditary ; genetics ; pathology ; Extracellular Matrix Proteins ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Transforming Growth Factor beta ; genetics

Bietti crystalline retinal dystrophy is a rare, inherited disorder whose hallmark is the presence of retinal crystal deposits associated with later chorioretinal degeneration. This condition may rarely be complicated by the development of cystoid macular oedema leading to rapid visual decline. Currently, treatment options for this complication of Bietti dystrophy are limited and the visual prognosis is poor. Here, we present a case of cystoid macular oedema associated with Bietti dystrophy that was successfully diagnosed using multimodal imaging techniques including optical coherence tomography and fluorescein angiography. These modalities confirmed the diagnosis of macular oedema and excluded other possible causes of oedema such as choroidal neovascularisation. In this patient, cystoid macular oedema was resolved with oral acetazolamide therapy, a treatment that has not been previously reported in this context. Acetazolamide treatment resulted in oedema resolution and improvement in visual function, and can be considered a therapeutic option for other patients with Bietti dystrophy who develop cystoid macular oedema.
Acetazolamide/*administration & dosage ; Administration, Oral ; Adult ; Corneal Dystrophies, Hereditary/*drug therapy/pathology ; Diuretics/*administration & dosage ; Humans ; Macular Edema/*drug therapy/pathology ; Male ; Retinal Diseases/*drug therapy/pathology ; Tomography, Optical Coherence ; Treatment Outcome

OBJECTIVETo identify the mutations of BIGH3 gene in Chinese patients with corneal dystrophies.

METHODSPolymerase chain reaction in exon 4, exon 12 and direct DNA sequencing of BIGH3 gene were performed in fifteen patients with corneal dystrophies and ten normal individuals as controls.

RESULTSMutations in BIGH3 gene were detected in all the patients with corneal dystrophies. BIGH3 gene mutations were not found in normal subjects. Twelve patients with Avellino corneal dystrophy had the missense mutation R124H in the BIGH3 gene. Three patients with granular corneal dystrophy had the missense mutation R555W in the BIGH3 gene.

CONCLUSIONR124H and R555W mutations in BIGH3 gene were found in the patients with Avellino and granular corneal dystrophies. Avellino corneal dystrophy associated with the R124H mutation is the most common form in the corneal dystrophies resulting from BIGH3 gene mutations. Condons 124 and 555 are also the hot spots for the mutations in the BIGH3 gene in the Chinese patients with corneal dystrophies.

Adolescent ; Adult ; Aged ; Base Sequence ; Corneal Dystrophies, Hereditary ; genetics ; pathology ; DNA ; chemistry ; genetics ; DNA Mutational Analysis ; Extracellular Matrix Proteins ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation, Missense ; Transforming Growth Factor beta ; genetics

No abstract available.
Asian Continental Ancestry Group ; Corneal Dystrophies, Hereditary/diagnosis/*genetics ; Cytochrome P450 Family 4/*genetics ; DNA Mutational Analysis ; Fluorescein Angiography ; Humans ; Male ; Middle Aged ; *Mutation ; Polymerase Chain Reaction ; Republic of Korea ; Retinal Diseases/diagnosis/*genetics ; Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence ; Visual Acuity