Evidence of mild founder mutations causing nemaline myopathy 10 in Germany and Austria.

Objective: To expand the clinical and genetic spectrum of nemaline myopathy 10 by a series of Austrian and German patients with a milder disease course and missense mutations in .

Methods: We characterized the clinical features and the genetic status of 4 unrelated adolescent or adult patients with nemaline myopathy.

Results: The 4 patients showed a relatively mild disease course.

An ex vivo RNA trans-splicing strategy to correct human generalized severe epidermolysis bullosa simplex.

Background: Generalized severe epidermolysis bullosa simplex (EBS-gen sev) is a genetic blistering skin disease in which autosomal dominant mutations in either the keratin KRT5 or KRT14 genes lead to impaired function of the intermediate filament cytoskeleton in the basal epidermis. Here we present an ex vivo RNA trans-splicing-based therapeutic approach to correct the phenotype.

Objectives: To correct a mutation within exon 1 of the KRT14 gene, using a 5'-trans-splicing approach, where any mutation within the first seven exons could be replaced by a single therapeutic molecule.

Cerebral localized marginal zone lymphoma presenting as hypothalamic-pituitary region disorder.

Introduction: Marginal zone B-cell lymphoma is a rare disease which can be considerably difficult to recognize and diagnose when signs of systemic involvement are absent.

Case Presentation: We report the case of a 57-year-old woman with initial olfactory disturbance, followed by psychosis, diabetes insipidus and hypothalamic eating disorder as an uncommon clinical presentation of marginal zone B-cell lymphoma.

Conclusion: Marginal zone B-cell lymphoma should be considered as a potential differential diagnosis in patients with hypothalamic disturbances.

Danon disease: case report and detection of new mutation.

Danon disease is an X-linked disorder resulting from mutations in the lysosome-associated membrane protein-2 (LAMP2) gene. We report a male patient with skeletal myopathy, mental retardation, and massive hypertrophic obstructive cardiomyopathy necessitating heart transplantation. Immunohistochemistry of skeletal muscle and leukocytes, western blot analysis of leukocytes and cardiac muscle, flow cytometry, and DNA sequencing were performed.

Novel KIND1 gene mutation in Kindler syndrome with severe gastrointestinal tract involvement.

Background: Kindler syndrome (online Mendelian Inheritance in Man No. 173650) is an autosomal recessive genodermatosis characterized by acral trauma-induced blistering that improves with age and by progressive poikiloderma in later life. Other clinical features include photosensitivity, webbing of the fingers and toes, nail dystrophy, periodontal disease, and mucosal alterations.

A novel sporadic mutation G14739A of the mitochondrial tRNA(Glu) in a girl with exercise intolerance.

We describe a 7-year-old girl who presented with loss of appetite, weakness and excercise intolerance. Enzyme investigation of the respiratory chain in muscle tissue revealed a combined complex I, III and IV deficiency. A novel heteroplasmic G-->A exchange at nucleotide position 14739 was found in the MTTE gene of the tRNA glutamic acid.

Deficiency of mitochondrial ATP synthase of nuclear genetic origin.

We present clinical and laboratory data from 14 cases with an isolated deficiency of the mitochondrial ATP synthase (7-30% of control) caused by nuclear genetic defects. A quantitative decrease of the ATP synthase complex was documented by Blue-Native electrophoresis and Western blotting and was supported by the diminished activity of oligomycin/aurovertin-sensitive ATP hydrolysis in fibroblasts (10 cases), muscle (6 of 7 cases), and liver (one case). All patients had neonatal onset and elevated plasma lactate levels.

[Dental alterations in junctional epidermolysis bullosa--report of a patient with a mutation in the LAMB3-gene].

During early odontogenesis the basement membrane is known to be important in epithelio-mesenchymal interactions. Mutations in the gene of one of the major structural proteins of the basement membrane such as laminin 5 might therefore be expected either to seriously compromise ameloblast differentiation and/ or interfere with normal basement-membrane formation and degradation and thus the binding of the ameloblasts to their underlying matrix. Teeth of patients suffering from junctional epidermolysis bullosa (JEB) can be severely affected by abnormal dental development and generalized or focal enamel hypoplasia.

Characteristic immunohistochemical and ultrastructural findings indicate that Kindler's syndrome is an apoptotic skin disorder.

Background: Kindler's syndrome is a rare genodermatosis mainly characterized by the onset of skin blistering in early childhood, web formation of fingers and toes, photosensitivity, and progressive poikiloderma. There is still debate whether this disease represents a distinctive entity in the spectrum of congenital bullous poikilodermas or a variant of dystrophic epidermolysis bullosa.

Objective: To evaluate the recently proposed and debated characteristic immunohistochemical and ultrastructural features of Kindler's syndrome.

Feline orthopoxvirus infection transmitted from cat to human.

We report the case of a 56-year-old female patient who presented with an inflamed, ulcerated lesion on the left side of her neck after contact (scratch) with a cat living in the patient's house. Satellite lesions developed despite local treatment and parenteral clindamycin. Histopatholgic examination and the Tzanck test showed evidence of a viral infection.

[Amniotic membrane transplantation with limbal stem cell transplantation as a combined procedure for corneal surface reconstruction after severe thermal or chemical burns].

Background: Severe thermal and chemical burns may result in limbal deficiency leading to persistent epithelial defects, complete conjunctival epithelial ingrowth and vascularisation of the cornea. If sufficiently severe, these burns may lead to very significant visual impairment. Amniotic membrane transplantation with limbal transplantation has recently been proposed as a new method for corneal surface reconstruction.

Histopathology of human corneas after amniotic membrane and limbal stem cell transplantation for severe chemical burn.

Purpose: To describe the histopathologic changes in the cornea following amniotic membrane transplantation (AMT) combined with limbal transplantation.

Methods: Four eyes with complete limbal stem cell deficiency after severe chemical burn underwent AMT with either a living-related conjunctival limbal allograft (lr-CLAL) (three eyes) or a conjunctival limbal autograft (CLAU) (one eye) for ocular surface reconstruction. Penetrating keratoplasty was performed several months after the initial procedure for further visual rehabilitation.

Eurosol versus fetal bovine serum-containing corneal storage medium.

Purpose: To evaluate the usability of Eurosol, a new medium-term corneal storage medium without components of bovine origin.

Methods: Ten pairs of human donor corneas were placed in tissue culture at 31 degrees C for 7, 14, 21, 28, or 35 days. One cornea of each pair was cultivated in conventional storage medium on Earls' minimum essential medium base containing 2% fetal bovine serum; the other one was stored in Eurosol.

A compound heterozygous one amino-acid insertion/nonsense mutation in the plectin gene causes epidermolysis bullosa simplex with plectin deficiency.

Plectin is a cytoskeleton linker protein expressed in a variety of tissues including skin, muscle, and nerves. Mutations in its gene are associated with epidermolysis bullosa simplex with late-onset muscular dystrophy. Whereas in most of these patients the pathogenic events are mediated by nonsense-mediated mRNA decay, the consequences of an in-frame mutation are less clear.

Recurrent keratoconus in a patient with Leber congenital amaurosis.

Purpose: Clinical history of a 17-year-old patient with Leber congenital amaurosis (LCA) with histologically proven recurrent keratoconus (KC) two years after corneal transplantation in one eye and a recurrence-like appearance with a more global contour on the other eye four years after corneal grafting is reported. The possible mechanisms for this recurrence are discussed in light of the fact that this is, to the best of our knowledge, the first penetrating keratoplasty reported in LCA.

Methods: Computerized videokeratography (CVKG) and specular microscopy were performed preoperatively.

Corneal lathing using the excimer laser and a computer-controlled positioning system.

Purpose: To present the excimer laser corneal shaping system (ELCS-S), an add-on device to the Keratom, a commercially available 193-nm excimer laser built by Schwind.

Methods: The system is designed for the preparation of donor corneas under sterile conditions using the ultraviolet laser to offer greatest possible flexibility. Lenticules for planolamellar grafting and refractive epikeratoplasty, as well as donor buttons for penetrating keratoplasty can be computer-designed by the surgeon or technician and lathed with the system.

Ocular involvement in IgA-epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is an autoimmune bullous disease with frequent ocular involvement, but visual loss is rare. In contrast, EBA patients with predominant IgA autoantibodies more frequently develop severe ocular involvement, which tends to be refractory to therapy. We report two patients with 'IgA-EBA' with ocular involvement.

A Turner-like phenotype in a girl with an isodicentric fluorescent Y chromosome mosaicism.

Background: The Ullrich-Turner syndrome (UTS) demonstrates a great clinical variability according to the cytogenetic and molecular genetic findings in various tissues. In few cases the karyotype reveals the presence of an additional Y-bearing cell line which is referred to as a borderline case of mixed gonadal dysgenesis. In this condition, Turner specific stigmata occur in about half of the cases.