Phenotypic diversity and mutation spectrum in hypotrichosis with juvenile macular dystrophy.

Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by abnormal growth of scalp hair during infancy, and by the later occurrence of macular degeneration leading to blindness during the first to third decade of life. Hypotrichosis with juvenile macular dystrophy was recently shown to result from mutations in CDH3 encoding P-cadherin. In this study, we assessed 27 individuals, including nine patients, belonging to five families in an attempt to characterize further the CDH3 mutation spectrum and delineate possible phenotype-genotype correlations.

The spirochetal chpK-chromosomal toxin-antitoxin locus induces growth inhibition of yeast and mycobacteria.

Toxin-antitoxin systems encoded by bacterial plasmids and chromosomes typically consist of a toxin that inhibits growth of the host cell and a specific antitoxin. In this report, the chpK gene from the chromosomal toxin-antitoxin locus of the spirochete Leptospira interrogans was studied in both prokaryotic and eukaryotic systems. Cloning of the the spirochetal chpK gene into a mycobacterial expressing vector led to dramatic reductions of transformation efficiency in both Mycobacterium smegmatis and Mycobacterium bovis BCG.

Type 1 segmental manifestation of Hailey-Hailey disease.

Two types of mosaic manifestations can be distinguished in autosomal dominant skin disorders. A type-1 mosaicism reflects a localized postzygotic mutation in an otherwise normal embryo. This mutation leads to a localized population of heterozygous cells, resulting in segmental disease.

The relation between the clinical subtypes of delirium and the urinary level of 6-SMT.

Delirium is a common syndrome among hospitalized elderly patients. In humans, sleep and circadian rhythms are disturbed during delirium, and both are influenced by the hormone melatonin. This prompted us to investigate the relationship of the clinical subtypes of delirium: 1).

Analysis of microsatellites in 13 hemiascomycetous yeast species: mechanisms involved in genome dynamics.

We have analyzed all di-, tri-, and tetranucleotide repeats in the partially sequenced genomes of 13 hemiascomycetous yeast species, and compared their sequences, lengths, and distributions to those observed in the genome of Saccharomyces cerevisiae. We found that most of the 13 species exhibit a unique distribution of microsatellites, not correlated to the base composition of their genome. Species close to S.

[Choroidal neovascularisation in type II membranoproliferative glomerulonephritis, photodynamic therapy as a treatment option--a case report].

Background: Photodynamic therapy (PDT) is an established treatment in predominantly classic choroidal neovascularisation (CNV) in exudative age-related macular degeneration (AMD). Membranoproliferative glomerulonephritis (MPGN) type II leads to AMD-similar changes ("pseudo-AMD") of the fundus with CNV as a late complication. We report on a patient suffering from MPGN II and a classic CNV who was treated with PDT.

Reticular erythrokeratoderma: a new disorder of cornification.

Heritable disorders of cornification form a large, clinically and genetically heterogeneous group. Recent advances in molecular genetics provide for the first time the opportunity to reliably classify some of these disorders based on their underlying etiology. Many rare phenotypes, however, still remain unclassified and do not fit into established classification schemes.

[Incidence of ocular manifestations in patients with histologically confirmed systemic sarcoidosis].

Background: Intraocular findings in sarcoidosis were described by US studies with 35 % anterior uveitis, 25 % posterior uveitis and 20 - 30 % for late complications in case of first presentation. We report on the spectrum and diagnostic possibilities in 38 German patients.

Patients And Methods: 38 patients (68 eyes) aged 11 - 58 years (average 42.

Specific amino-acid residues in the N-terminus and TM3 implicated in channel function and oligomerization compatibility of connexin43.

To identify signals that convey connexin oligomerization compatibility, we have aligned amino-acid sequences of alpha and beta group connexins (Cx) and compared the physico-chemical properties of each homologous amino-acid residue. Four positions were identified that consistently differed between alpha and beta-type connexins; two are located in the N-terminal domain (P1 and P2, corresponding to residues 12 and 13 of the Cx43 sequence), and two in the third trans-membrane-spanning domain TM3 (P3 and P4, corresponding to residues 152 and 153 of the Cx43 sequence). Replacement of each of these residues in Cx43 (an alpha-type connexin) with the corresponding residues of Cx32 (a beta-type connexin) resulted in the assembly of all variants into gap junctions; however, only the P4 variant was functional, as indicated by lucifer yellow dye transfer assays.

[Testing central retinal function with multifocal electroretinography before and after photodynamic therapy].

Background: Photodynamic therapy (PDT) is applied for certain forms of choroidal neovascular membrane (CNV). The aim of this study was to investigate the effect of PDT on central retinal function as assessed by multifocal electroretinography (ERG).

Methods: 24 patients (25 eyes) with CNV (>50% classic 12 eyes) or occult (9 eyes) in age related macular degeneration (AMD) and CNV with pathological myopia (4 eyes) were treated by PDT using Verteporfin((R)).

[Therapy of normal tension glaucoma: effect of brinzolamide on ocular haemodynamics].

Background: Altered ocular perfusion plays a role in the pathophysiology of normal tension glaucoma. Dorzolamide, a locally applied inhibitor of carbonic anhydrase, is thought to increase ocular blood flow. Less data are available regarding the influence exercised on ocular perfusion by brinzolamide, another and different, locally administered, inhibitor of carbonic anhydrase.

Divergent effects of two sequence variants of GJB3 (G12D and R32W) on the function of connexin 31 in vitro.

Recently, we identified several missense mutations of the connexin gene GJB3 encoding connexin 31 (Cx31) in erythrokeratodermia variabilis (EKV), an autosomal dominant skin disorder. These mutations include G12D, which replaces a conserved glycine residue in the amino-terminus of Cx31 and is associated with a severe EKV phenotype. In contrast, the biologic relevance of the GJB3 sequence variant R32W located in the first transmembrane domain of Cx31 is disputed.

[Estimation of ocular perfusion: a practical oriented comparison of different methods].

Background: Ocular haemodynamics play a prominent part in many ocular diseases. This leads to the need to determine ocular perfusion. Several studies reveal advantages of colour Doppler imaging (CDI) in ophthalmologic diagnostics.

Glucosylation of alpha-butyl- and alpha-octyl-D-glucopyranosides by dextransucrase and alternansucrase from Leuconostoc mesenteroides.

For the first time, glucosylation of alpha-butyl- and alpha-octylglucopyranoside was achieved using dextransucrase (DS) of various specificities, and alternansucrase (AS) from Leuconostoc mesenteroides. All the glucansucrases (GS) tested used alpha-butylglucopyranoside as acceptor; in particular, DS produced alpha-D-glucopyranosyl-(1-->6)-O-butyl-alpha-D-glucopyranoside and alpha-D-glucopyranosyl-(1-->6)-alpha-D-glucopyranosyl-(1-->6)-O-butyl-alpha-D-glucopyranoside. In contrast, alpha-octylglucopyranoside was glucosylated only by AS which was shown to be the most efficient catalyst.

Epidermolytic hyperkeratosis and epidermolysis bullosa simplex caused by frameshift mutations altering the v2 tail domains of keratin 1 and keratin 5.

The cytoskeleton of epithelial cells is formed by heteropolymeric keratin proteins characterized by a central alpha-helical rod flanked by nonhelical head and tail domains of variable sequence. Most mutations described in 18 distinct keratins disrupt highly conserved regions at the boundaries of the rod, which have been recognized as zones of overlap during keratin alignment and assembly into intermediate filaments. We recently reported the first mutation located in a keratin tail domain (V2) in ichthyosis hystrix Curth-Macklin.

Genetic heterogeneity in erythrokeratodermia variabilis: novel mutations in the connexin gene GJB4 (Cx30.3) and genotype-phenotype correlations.

Erythrokeratodermia variabilis is an autosomal dominant genodermatosis characterized by persistent plaque-like or generalized hyperkeratosis and transient red patches of variable size, shape, and location. The disorder maps to a cluster of connexin genes on chromosome 1p34-p35.1 and, in a subset of families, results from mutations in the gene GJB3 encoding the gap junction protein connexin-31 (Cx31).

Contractions and expansions of CAG/CTG trinucleotide repeats occur during ectopic gene conversion in yeast, by a MUS81-independent mechanism.

CAG/CTG trinucleotide repeat tracts expand and contract at a high rate during gene conversion in Saccharomyces cerevisiae. In order to characterize the mechanism responsible for such rearrangements, we built an experimental system based on the use of the rare cutter endonuclease I-SceI, to study the fate of trinucleotide repeat tracts during meiotic or mitotic (allelic or ectopic) gene conversion. After double-strand break (DSB) induced meiotic recombination, (CAG)(98) and (CAG)(255) are rearranged in 5% and 52% of the gene conversions, respectively, with similar proportions of contractions and expansions.

A novel homozygous nonsense deletion/insertion mutation in the keratin 14 gene (Y248X; 744delC/insAG) causes recessive epidermolysis bullosa simplex type Köbner.

We report the sixth case of a human keratin 14 'knockout' mutation resulting in recessive epidermolysis bullosa simplex (EBS). A novel, homozygous nonsense mutation resulting from a deletion/insertion mutation (744delC/insAG) leads to a premature termination codon in the KRT14 gene (Y248X). The patient suffers from generalized cutaneous blistering since birth, mild nail dystrophy, involvement of mucous membranes and multiple epidermolysis bullosa naevi.

A missense mutation in CDH3, encoding P-cadherin, causes hypotrichosis with juvenile macular dystrophy.

Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by early hair loss heralding severe degenerative changes of the retinal macula and culminating in blindness during the second to third decade of life. Recently, we identified a frameshift mutation in the CDH3 gene encoding P-cadherin as the proximal cause of hypotrichosis with juvenile macular dystrophy in four families. We report here another consanguineous family in which four members were diagnosed with hypotrichosis with juvenile macular dystrophy.

[Rheophoresis. A systematic approach to therapy of age-related macular degeneration (AMD)?].

Background: Choroidal microcirculation is impaired in age-related macular degeneration (AMD), and leads to deposition of lipids and proteins in Bruch's membrane. Rheophoresis can improve choroidal microcirculation by eliminating high molecular weight, rheologically relevant plasma proteins. The objective of this post-certification study was to analyse the effect of rheophoresis in 10 AMD patients.

Cat scratch disease and acute rejection after pediatric renal transplantation.

Cat scratch disease (CSD) can lead to unexplained fever, generalized lymphadenopathy and organomegaly in immunocompetent individuals. CSD has rarely been reported in immunocompromised transplant recipients, where its clinical features would mimic the more common post-transplant lymphoproliferative disease (PTLD). We report three cases of CSD seen recently in children who had received prior kidney transplants.