[Hereditary gelsolin amyloidosis--40 years of Meretoja disease].

Hereditary gelsolin amyloidosis is an autosomally dominantly inherited systemic disease, first described in 1969 by the Finnish ophthalmologist Jouko Meretoja. The estimated number of disease carriers in Finland is almost 1 000, and the disease has subsequently been found in many other countries as well. It's typical initial manifestation is lattice corneal dystrophy, detected at biomicroscopic examination of the eye by the age of 25 to 30 years, followed by slowly progressing cranial neuropathy with bilateral facial palsy, polyneuropathy and generalized cutis laxa.

Genotype of lattice corneal dystrophy (R124C mutation in TGFBI) in a patient presenting with features of avellino corneal dystrophy.

Purpose: To present a patient with a genotype usually associated with lattice corneal dystrophy but with clinical and histopathologic features of advanced Avellino corneal dystrophy.

Methods: Penetrating keratoplasty was performed with subsequent histopathologic analysis. For genetic testing, a 5-mL blood sample was taken after informed consent.

TGFBI gene mutation analysis in a Chinese pedigree of Reis-Bücklers corneal dystrophy.

Purpose: To analyze transforming growth factor beta-induced (TGFBI) gene mutations in a Chinese pedigree with Reis-Bücklers dystrophy (RBCD).

Methods: In a four-generation Chinese family with Reis-Bücklers dystrophy, six members were patients and the rest were unaffected. All members of the family underwent complete ophthalmologic examinations.

Lattice corneal dystrophy type IV (p.Leu527Arg) is caused by a founder mutation of the TGFBI gene in a single Japanese ancestor.

Purpose: Lattice corneal dystrophy (LCD) type IV (LCD4) is a late-onset corneal dystrophy with amyloid deposition at the deep stromal layer of cornea. As with other corneal dystrophies, this LCD subtype is also caused by a mutation (p. Leu527Arg) of the transforming growth factor, beta-induced (TGFBI) gene.

Hereditary amyloidosis of the Finnish type in a German family: clinical and electrophysiological presentation.

Hereditary amyloidosis of the Finnish type (HAF, or familial amyloid polyneuropathy type IV) is an autosomal dominant disease that has been described most commonly in the Finnish population but has also been found in some other countries. Herein we report the first German family whose members suffer from this condition. There are no known Finnish ancestors.

Fungal keratitis in lattice dystrophy.

We report a case of fungal keratitis occurring in a patient with lattice dystrophy. A 57-year-old farmer presented with a corneal ulcer following probable entry of paddy husk in the right eye, of one month duration. Corneal scraping revealed pigmented fungal filaments while culture grew Alternaria alternata.

Novel and known mutations of TGFBI, their genotype-phenotype correlation and structural modeling in 3 Chinese families with lattice corneal dystrophy.

Purpose: To report novel transforming growth factor beta-induced (TGFBI) mutations responsible for lattice corneal dystrophy (LCD), the associated genotype-phenotype correlation, and structural changes in the mutant proteins in three Chinese families.

Methods: Three unrelated Chinese families were diagnosed as Type I LCD. Mutations in TGFBI were detected by sequencing all of the 17 exons and splice sites of the gene.

Detection of the most common corneal dystrophies caused by BIGH3 gene point mutations using a multispot gold-capped nanoparticle array chip.

The localized surface plasmon resonance (LSPR) optical property has recently been well employed as an effective platform for the quantitative detection of protein-protein interactions on the nanoscale. However, its advantage has not been fully explored yet in the DNA diagnosis field, especially in detecting point mutations of DNA. Point mutations of the BIGH3 gene are associated with the most common corneal dystrophies (CDs), such as Avellino corneal dystrophy, Reis-Bucklers corneal dystrophy, and lattice corneal dystrophy.

A novel mutation I522N within the TGFBI gene caused lattice corneal dystrophy I.

Purpose: To identify mutations within the TGFBI gene in a Chinese family with lattice corneal dystrophy type I (LCD I).

Methods: Genomic DNA of three affected, four unaffected family members and 50 normal individuals was extracted from peripheral leukocytes. All exons of TGFBI were amplified by polymerase chain reaction (PCR) methods and direct sequencing was carried out for mutation analysis.

TGFBI mutational analysis in a New Zealand population of inherited corneal dystrophy patients.

Aim: The corneal dystrophies represent a group of clinically and genetically heterogeneous, inherited diseases, often resulting in bilateral opacification of the cornea, and may require penetrating keratoplasty. Mutations in the transforming growth factor beta-induced (TGFBI) gene segregate with a wide range of phenotypically heterogeneous corneal dystrophies. Many of the other dystrophies remain without molecular characterisation.

Lattice corneal dystrophy, gelsolin type (Meretoja's syndrome).

Purpose: This paper reviews current knowledge about the pathogenesis, clinical manifestations and treatment of lattice corneal dystrophy, gelsolin type (LCD2, Meretoja's syndrome).

Methods: Material is derived from literature searches, a case study of a Finnish patient living in Sweden, and interviews in Helsinki with Professor Ahti Tarkkanen and Dr Sari Kiuru-Enari, both of whom have extensive first-hand experience in treating patients with the disease.

Results: The disease is now reported from several countries in Europe, as well as Japan, the USA and Iran.

Hereditary gelsolin amyloidosis mimicking Sjögren's syndrome.

Hereditary gelsolin amyloidosis (AGel amyloidosis) belongs to the wide group of amyloidotic diseases, which comprise various hereditary but also sporadic forms, such as inflammation-associated AA amyloidosis, primary or myeloma-associated AL amyloidosis and common Alzheimer's disease and type II diabetes-associated local amyloidoses. AGel amyloidosis caused by a gelsolin G654A gene mutation is autosomally dominantly inherited and presents typically in the 30s with progressive corneal lattice dystrophy, followed by cutis laxa and cranial polyneuropathy. Here, we present a case of sicca syndrome, originally diagnosed as primary Sjögren's syndrome (SS) but later found to represent an initial disease manifestation of AGel amyloidosis, not recognised earlier.

Femtosecond-assisted lamellar keratoplasty in atypical Avellino corneal dystrophy of Indian origin.

Purpose: To report a case of Avellino corneal dystrophy (ACD) in a patient of Indian origin treated with femtosecond-assisted lamellar keratoplasty (FALK).

Methods: A 6-year-old male patient presented with severe photophobia with decreased vision for 2 months. A clinical diagnosis of Avellino dystrophy was made after complete examination under anesthesia and FALK was performed.

The survival of donor-derived cells in a successfully grafted corneal button 10 years after penetrating keratoplasty for lattice dystrophy.

Aims: To investigate the survival of donor-derived cells in a successfully grafted corneal button 10 years after penetrating keratoplasty for lattice dystrophy.

Methods: In 1996, a 48-year-old male with lattice corneal dystrophy underwent penetrating keratoplasty 3 times in the right eye within a 3-month interval. Nine years and 7 months later, the patient underwent a fourth penetrating keratoplasty.

Severe ataxia with neuropathy in hereditary gelsolin amyloidosis.

Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder caused by a G654A or G654T gelsolin mutation, reported from Europe, North America, and Japan. Principal clinical signs are corneal lattice dystrophy, cutis laxa and cranial neuropathy, often deleterious at advanced age. Peripheral neuropathy, if present, is usually mild.

Double mutation (R124H, N544S) of TGFBI in two sisters with combined expression of Avellino and lattice corneal dystrophies.

Purpose: The R124H mutation of the keratoepithelin gene (TGFBI) causes Avellino corneal dystrophy whereas the N544S mutation of this same gene gives rise to lattice corneal dystrophy. We now report two cases with both R124H and N544S mutations of TGFBI.

Methods: Genomic DNA and cDNA were isolated from the proband and family members and were subjected to polymerase chain reaction-mediated amplification of exons 1-17 of TGFBI.

Familial amyloid polyneuropathy (Finnish type) presenting multiple cranial nerve deficits with carpal tunnel syndrome and orthostatic hypotension.

Familial amyloid polyneuropathy, Finnish type (FAF), is a dominantly inherited disorder caused by mutations in the gelsolin gene and rarely reported in several countries. We report a Japanese FAF patient with a missense mutation (G654A), presenting multiple cranial nerve symptoms, corneal lattice dystrophy, carpal tunnel syndrome and orthostatic hypotension. It is notable that this patient showed very wide range of cranial nerve involvement (III, IV, VI, VII, VIII, IX, X and XII), which have gradually deteriorated for 6 years.

[TGFBI gene mutations in three Chinese families with autosomal dominant corneal dystrophy].

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

Methods: Analysis 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.

Results: Three 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.

Clinical and genetic features of TGFBI-linked corneal dystrophies in Mexican population: description of novel mutations and novel genotype-phenotype correlations.

Corneal dystrophies (CDS) are inherited disorders characterized by an altered corneal transparency and refractive index which may be caused by a progressive accumulation of deposits within the different corneal layers. Most CDs are inherited in an autosomal dominant fashion and mutations in the TGFBI gene at chromosome 5q31 cause the majority of CDs affecting the stromal layer. A genotype-phenotype correlation has been identified in most analyzed populations as specific amino acid changes in TGFBI protein cause specific stromal phenotypes.

Alterations of epithelial adhesion molecules and basement membrane components in lattice corneal dystrophy (LCD).

Background: The aim of the study was to investigate the histopathological and ultrastructural correlate of delayed epithelial healing in eyes with lattice corneal dystrophy (LCD).

Materials And Methods: Corneal buttons from 4 patients with LCD (two with subepithelial, two with stromal amyloid deposits) and 2 control corneas were examined. Cell-matrix adhesion molecules and basement membrane components of the corneal epithelium were analyzed by immunohistochemistry and hemidesmosomes between epithelium and stroma were quantified by transmission electron microscopy (TEM).

Endogenous calpain-3 activation is primarily governed by small increases in resting cytoplasmic [Ca2+] and is not dependent on stretch.

Proteolytically active calpain-3/p94 is clearly vital for normal muscle function, since its absence leads to limb girdle muscular dystrophy 2A, but its function and regulatory control are poorly understood. Here we use single muscle fibers, individually skinned by microdissection, to investigate the diffusibility and autolytic activation of calpain-3 in situ. Virtually all calpain-3 present in mature muscle fibers is tightly bound in the vicinity of the titin N2A line and triad junctions and remains so irrespective of fiber stretching or raised [Ca(2+)].

Corneal melt in lattice corneal dystrophy type II after cataract surgery.

We report a patient with lattice corneal dystrophy type II, also known as Meretoja syndrome or familial amyloidosis Finnish type, who developed a corneal melt 15 days after uneventful phacoemulsification. Despite conservative treatment, the corneal melt resulted in perforation. Uneventful penetrating keratoplasty was performed, but delayed graft epithelial healing was noticed postoperatively.

Classic lattice corneal dystrophy associated with monoclonal gammopathy after exclusion of a TGFBI mutation.

Purpose: The purpose of this study was to report the association of phenotypic features characteristic of lattice corneal dystrophy (LCD) with a monoclonal gammopathy of undetermined significance (MGUS) after exclusion of a coding region mutation in transforming growth factor beta-induced (TGFBI) gene.

Design: Case report.

Methods: Slit-lamp examination and collection of DNA for TGFBI screening were performed.