BACKGROUNDMutations in the transforming growth factor beta I (TGFBI) gene cause several types of autosomal-dominant corneal dystrophies. We investigated the role of this gene in a Chinese family affected by granular corneal dystrophy (GCD).

METHODSFamily history and phenotypic data were recorded. The diagnosis of GCD was made on the basis of clinical evaluation. The genomic DNA was extracted from peripheral blood leukocytes. All the exons and flanking intron-exon boundary sequences of TGFbetaI were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing.

RESULTSA heterozygous C to T transition at nucleotide c.1663 (CGG to TGG R555W) of TGFbetaI gene was present in two affected members but was absent in the rest of the family members.

CONCLUSIONA recurrent pathogenic R555W of TGFbetaI gene mutation is identified, which appears to be the predominant mutations causing GCD in different populations.

Adult ; Corneal Dystrophies, Hereditary ; genetics ; Female ; Humans ; Middle Aged ; Mutation ; Transforming Growth Factor beta1 ; genetics

A 43-year-old man developed decreased vision in the right eye that had persisted for seven years. Under slit lamp examination, corneal clouding was noted with normal endothelium and ocular structure. From the clinical evidence, we suspected that the patient had congenital hereditary stromal dystrophy (CHSD). He and his family underwent a genetic analysis. Penetrating keratoplasty was conducted, and the corneal button was investigated for histopathologic confirmation via both light and electron microscopy. The histopathologic results revealed mildly loosened stromal structures, which exhibited an almost normal arrangement and differed slightly from the previous findings of CHSD cases. With regard to the genetic aspects, the patient and his mother harbored a novel point mutation of the decorin gene. This genetic mutation is also distinct from previously described deletion mutations of the decorin gene. This case involved delayed penetration of mild clinical symptoms with the histological feature of a loosened fiber arrangement in the corneal stroma. We concluded that this condition was a mild form of CHSD. However, from another perspective, this case could be considered as "decorin gene-associated corneal dystrophy," which is distinct from CHSD. Further evaluation will be required for appropriate clinical, histopathologic and genetic approaches for such cases.
Adult ; Corneal Dystrophies, Hereditary/diagnosis/*genetics ; Decorin/*genetics ; Humans ; Male ; Microscopy, Electron ; Pedigree ; *Point Mutation ; Republic of Korea

OBJECTIVETo analyze the clinical features and TGFBI gene mutation in a Chinese family affected with Reis-Bucklers corneal dystrophy.

METHODSGenomic DNA was extracted from 53 members including 9 patients from the family. The 17 exons and splice region of introns of the TGFBI gene were amplified by PCR and directly sequenced. All family members were subjected to ophthalmologic examination.

RESULTSA heterozygous mutation (R124L) was found in exon 4 of the TGFBI gene among all patients from the family. The same mutation was not found among unaffected family members. The inheritance pattern of the family was identified as autosomal dominant, and the Reis-Bucklers corneal dystrophy in the family was diagnosed as the geographic type.

CONCLUSIONThe R124L mutation of the TGFBI gene probably underlies the pathogenesis of Reis-Bucklers corneal dystrophy in this Chinese family. Molecular genetic approach is useful for the proper diagnosis of this type of corneal dystrophy.

Corneal Dystrophies, Hereditary ; etiology ; genetics ; Female ; Humans ; Male ; Mutation ; Sequence Analysis, DNA ; Transforming Growth Factor beta1 ; genetics

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

Gelatinous drop-like corneal dystrophy (GDLD) is an autosomal recessive hereditary disease, which may result in bilateral loss of vision. The gene responsible for GDLD, M1S1 is mapped on the short arm of chromosome 1 (1p), but the possible etiology of this disease remains unclear. Corneal transplantation is the only treatment for visual rehabilitation. The detection of the mutations of the M1S1 gene and the possible etiological involvement of the amyloid deposits are discussed. The current literatures are extensively reviewed in this article.
Antigens, Neoplasm ; genetics ; Cell Adhesion Molecules ; genetics ; Chromosomes, Human, Pair 1 ; genetics ; Corneal Dystrophies, Hereditary ; diagnosis ; genetics ; therapy ; DNA Mutational Analysis ; Epithelial Cell Adhesion Molecule ; Humans ; Mutation

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

To report a novel mutation within the CHST6 gene, as well as describe light and electron microscopic features of a case of macular corneal dystrophy. A 59-year old woman with macular corneal dystrophy in both eyes who had decreased visual acuity underwent penetrating keratoplasty. Further studies including light and electron microscopy, as well as DNA analysis were performed. Light microscopy of the cornea revealed glycosaminoglycan deposits in the keratocytes and endothelial cells, as well as extracellularly within the stroma. All samples stained positively with alcian blue, colloidal iron, and periodic acid-Schiff. Electron microscopy showed keratocytes distended by membrane-bound intracytoplasmic vacuoles containing electron-dense fibrillogranular material. These vacuoles were present in the endothelial cells and between stromal lamellae. Some of the vacuoles contained dense osmophilic whorls. A novel homozygous mutation (c.613 C>T [p.Arg205Trp]) was identified within the whole coding region of CHST6. A novel CHST6 mutation was detected in a Korean macular corneal dystrophy patient.
Corneal Dystrophies, Hereditary/diagnosis/*genetics/metabolism ; Corneal Keratocytes/ultrastructure ; DNA/*genetics ; DNA Mutational Analysis ; Female ; Humans ; Microscopy, Electron ; Middle Aged ; *Mutation, Missense ; Pedigree ; Polymerase Chain Reaction ; Republic of Korea ; Sulfotransferases/*genetics/metabolism

An 87-year-old woman visited our clinic for a scheduled cataract surgery. At the time of preoperative evaluation, slit lamp examination showed lattice-shaped and granular deposits with asymmetrical patterns in the stroma of both corneas. Genomic DNA samples of the patient, amplified by polymerase chain reaction, showed a single nucleotide substitution, c. 1580T>G (p.L527R), in the transforming growth factor-beta-induced TGFBI gene. We also found two additional SNP mutations, c.1620T>C (p.F540F) and c.1678+23G>A, along with the well-known L527R mutation. This is the first report of lattice corneal dystrophy type IV with an L527R mutation outside of Japan, and could challenge the idea that L527R is caused by a mutation from a single Japanese ancestor.
Aged, 80 and over ; Corneal Dystrophies, Hereditary/diagnosis/*genetics/metabolism ; DNA/*genetics ; DNA Mutational Analysis ; Extracellular Matrix Proteins/*genetics/metabolism ; Female ; Humans ; *Mutation ; Pedigree ; Polymerase Chain Reaction ; Transforming Growth Factor beta/*genetics/metabolism

An 87-year-old woman visited our clinic for a scheduled cataract surgery. At the time of preoperative evaluation, slit lamp examination showed lattice-shaped and granular deposits with asymmetrical patterns in the stroma of both corneas. Genomic DNA samples of the patient, amplified by polymerase chain reaction, showed a single nucleotide substitution, c. 1580T>G (p.L527R), in the transforming growth factor-beta-induced TGFBI gene. We also found two additional SNP mutations, c.1620T>C (p.F540F) and c.1678+23G>A, along with the well-known L527R mutation. This is the first report of lattice corneal dystrophy type IV with an L527R mutation outside of Japan, and could challenge the idea that L527R is caused by a mutation from a single Japanese ancestor.
Aged, 80 and over ; Corneal Dystrophies, Hereditary/diagnosis/*genetics/metabolism ; DNA/*genetics ; DNA Mutational Analysis ; Extracellular Matrix Proteins/*genetics/metabolism ; Female ; Humans ; *Mutation ; Pedigree ; Polymerase Chain Reaction ; Transforming Growth Factor beta/*genetics/metabolism