A common NYX mutation in Flemish patients with X linked CSNB

Aims: The Schubert-Bornschein type of complete congenital stationary night blindness (CSNB) is a genetically heterogeneous retinal disorder. It is characterised by a non-progressive disease course, often associated with high myopia and nystagmus. So far, mutations in two genes, NYX (nyctalopin) and GRM6 (metabotropic glutamate receptor 6) have been associated with this form of CSNB. The purpose of this study was to identify the genetic defect in affected male patients from Flemish families with complete CSNB. Methods: Probands with CSNB from three large Flemish families underwent ophthalmological examination. DNA was extracted from peripheral blood, and the coding region of NYX along with parts of the 5'UTR and 3'UTR and intronic regions covering the splice sites were PCR amplified and sequenced. Results: In the affected individuals of three Flemish families with the complete form of CSNB a novel NYX mutation, c.855delG was identified. This deletion is predicted to lead to a frameshift mutation, p. Asp286ThrfsX62 causing a premature stop codon. Conclusion: Previously, both single families with different mutations in NYX as well as different families with an identical mutation, suggestive of a founder mutation, have been described. The c.855delG deletion in NYX seems to be a common mutation associated with CSNB in the Flemish population from Belgium. Thus, we suggest performing diagnostic testing for CSNB in the Flemish population initially directed towards the identification of this mutation. Subsequent screening for other mutations in NYX or GRM6 could be performed as a second step

Peripapillary Sparing With Near Infrared Autofluorescence Correlates With Electroretinographic Findings in Patients With Stargardt Disease

PURPOSE: To evaluate the correlation between the quantification of peripapillary sparing and electroretinogram (ERG) outcomes in autosomal recessive Stargardt disease (STGD1). METHODS: Near infrared fundus autofluorescence (NIR-FAF) images of 101 eyes of 101 patients were retrospectively reviewed. Peripapillary sparing was assessed both qualitatively and quantitatively. The area of spared tissue (AST) was calculated in a 1-mm-wide ring around the optic disc after binarization of the 55\ub0 NIR-FAF. These measurements were correlated with the presence of normal ERG (group I), abnormal photopic responses (group II), or abnormal photopic and scotopic responses (group III). RESULTS: AST showed significant correlations with ERG groups (R = -0.802, P < 0.001). While qualitative assessment of peripapillary sparing (i.e., present or not) also showed a significant correlation with ERG groups (R = -0.435, P < 0.001), it was weaker than by AST quantification. The ordinal regression analysis showed that the increase in AST was associated with a decrease in the odds of belonging to ERG groups II and III, with an odds ratio of 0.82 (95% confidence interval [CI] 0.78-0.87), P < 0.001. CONCLUSIONS: The AST around the optic disc in eyes with STGD1 correlates with the impairment of photoreceptors as shown in the ERG. If replicated in future longitudinal studies, the quantification of peripapillary sparing may prove to be a useful parameter for evaluating the visual prognosis of these eyes

Prevalence of ABCA4 Deep-Intronic Variants and Related Phenotype in An Unsolved "One-Hit" Cohort with Stargardt Disease

We investigated the prevalence of reported deep-intronic variants in a French cohort of 70 patients with Stargardt disease harboring a monoallelic pathogenic variant on the exonic regions of ABCA4. Direct Sanger sequencing of selected intronic regions of ABCA4 was conducted. Complete phenotypic analysis and correlation with the genotype was performed in case a known intronic pathogenic variant was identified. All other variants found on the analyzed sequences were queried for minor allele frequency and possible pathogenicity by in silico predictions. The second mutated allele was found in 14 (20%) subjects. The three known deep-intronic variants found were c.5196+1137G>A in intron 36 (6 subjects), c.4539+2064C>T in intron 30 (4 subjects) and c.4253+43G>A in intron 28 (4 subjects). Even though the phenotype depends on the compound effect of the biallelic variants, a genotype-phenotype correlation suggests that the c.5196+1137G>A was mostly associated with a mild phenotype and the c.4539+2064C>T with a more severe one. A variable effect was instead associated with the variant c.4253+43G>A. In addition, two novel variants, c.768+508A>G and c.859-245_859-243delinsTGA never associated with Stargardt disease before, were identified and a possible splice defect was predicted in silico. Our study calls for a larger cohort analysis including targeted locus sequencing and 3D protein modeling to better understand phenotype-genotype correlations associated with deep-intronic changes and patients' selection for clinical trials

Heißwasserextrahierbarer Kohlenstoff und Bodenatmung als Parameter zur Abschätzung der potentiellen Kohlenstofffreisetzung aus organischen Böden

Durch Ihre hohen Gehalte an Kohlenstoff (C) und organischer Bodensubstanz (OBS) und besitzen Moorböden eine herausragende Rolle im globalen Kohlenstoffkreislauf. Bei unsachgemäßer Nutzung setzen diese organischen Böden besonders hohe Mengen an C, z.B in Form von CO2 frei. Der labile und aktive Anteil der OBS, der potentiell besonders leicht freigesetzt werden kann, lässt sich allgemein mit dem Parameter heißwasserextrahierbarer Kohlenstoff (Chwe) abschätzen, da diese Fraktion große Mengen leicht umsetzbarer Bestandteile wie etwa hohe Anteile an mikrobieller Biomasse, Einfachzucker oder Ligninmonomere enthält. Bis jetzt ist aber unklar, wie gut sich dieser Parameter zur Ableitung der potentiellen C-Freisetzung aus Moorböden eignet. Für verschiedene Mineralböden konnten bereits enge Korrelationen zwischen dem Chwe und der jeweiligen Bodentamung aufgezeigt werden. Studien zur Beziehung der CO2-Freisetzung und dem Parameter Chwe speziell für organische Böden fehlen bisher. Ziel der vorliegenden Untersuchung war es deshalb, diese möglichen Korrelationen für organische Böden zu untersuchen. Dazu wurde der Chwe an über 50 unterschiedlichen Moorbodensubstraten ermittelt. Hier wurde eine Extraktionsmethode angewandt, welche speziell an die hohen Anteile an OBS angepasst wurde. Daneben wurde die jeweilige Bodenatmung mittels Inkubationsversuchen im Labor gemessen und mit dem Gehalt an Chwe verglichen. Die bisherigen Ergebnisse zeigen mittlere bis hohe Korrelationen zwischen der Bodenatmung und dem Chwe, so dass davon auszugehen ist, dass der Chwe zur Abschätzung einer potentiellen C-Freisetzung auch für organische Böden herangezogen werden kann, um damit die Empfindlichkeit gegenüber Kohlenstoffverlusten beschreiben zu können. Die gewonnenen Daten sollten allerdings durch zusätzliche Untersuchungen, vor allem an bisher nicht genügend berücksichtigten Moorbodensubstraten, weiter überprüft werden

Physical and hydrological properties of peat as proxies for degradation of South African peatlands: Implications for conservation and restoration

The physical and hydrological properties of peat from seven peatlands in northern Maputaland (South Africa) were investigated and related to the degradation processes of peatlands in different hydrogeomorphic settings. The selected peatlands are representative of typical hydrogeomorphic settings and different stages of human modification from natural to severely degraded. Nineteen transects (141 soil corings in total) were examined in order to describe peat properties typical of the distinct hydrogeomorphic settings. We studied degree of decomposition, organic matter content, bulk density, water retention, saturated hydraulic conductivity and hydrophobicity of the peats. From these properties we derived pore size distribution, unsaturated hydraulic conductivity and maximum capillary rise. We found that, after drainage, degradation advances faster in peatlands containing wood peat than in peatlands containing radicell peat. Eucalyptus plantations in catchment areas are especially threatening to peatlands in seeps, interdune depressions and unchannelled valley bottoms. All peatlands and their recharge areas require wise management, especially valley-bottom peatlands with swamp forest vegetation. Blocking drainage ditches is indispensable as a first step towards achieving the restoration of drained peatland areas, and further measures may be necessary to enhance the distribution of water. The sensitive swamp forest ecosystems should be given conservation priority

WDR34, a candidate gene for non-syndromic rod-cone dystrophy

Rod-cone dystrophy (RCD), also called retinitis pigmentosa, is characterized by rod followed by cone photoreceptor degeneration, leading to gradual visual loss. Mutations in over 65 genes have been associated with non-syndromic RCD explaining 60% to 70% of cases, with novel gene defects possibly accounting for the unsolved cases. Homozygosity mapping and whole-exome sequencing applied to a case of autosomal recessive non-syndromic RCD from a consanguineous union identified a homozygous variant in WDR34. Mutations in WDR34 have been previously associated with severe ciliopathy syndromes possibly associated with a retinal dystrophy. This is the first report of a homozygous mutation in WDR34 associated with non-syndromic RCD

Relative frequencies of inherited retinal dystrophies and optic neuropathies in Southern France: assessment of 21-year data management

PURPOSE: Inherited retinal dystrophies (IRDs) and inherited optic neuropathies (IONs) are rare diseases defined by specific clinical and molecular features. The relative prevalence of these conditions was determined in Southern France. METHODS: Patients recruited from a specialized outpatient clinic over a 21-year period underwent extensive clinical investigations and 107 genes were screened by polymerase chain reaction/sequencing. RESULTS: There were 1957 IRD cases (1481 families) distributed in 70% of pigmentary retinopathy cases (56% non-syndromic, 14% syndromic), 20% maculopathies and 7% stationary conditions. Patients with retinitis pigmentosa were the most frequent (47%) followed by Usher syndrome (10.8%). Among non-syndromic pigmentary retinopathy patients, 84% had rod-cone dystrophy, 8% cone-rod dystrophy and 5% Leber congenital amaurosis. Macular dystrophies were encountered in 398 cases (30% had Stargardt disease and 11% had Best disease). There were 184 ION cases (127 families) distributed in 51% with dominant optic neuropathies, 33% with recessive/sporadic forms and 16% with Leber hereditary optic neuropathy. Positive molecular results were obtained in 417/609 families with IRDs (68.5%) and in 27/58 with IONs (46.5%). The sequencing of 5 genes (ABCA4, USH2A, MYO7A, RPGR and PRPH2) provided a positive molecular result in 48% of 417 families with IRDs. Except for autosomal retinitis pigmentosa, in which less than half the families had positive molecular results, about 75% of families with other forms of retinal conditions had a positive molecular diagnosis. CONCLUSIONS: Although gene discovery considerably improved molecular diagnosis in many subgroups of IRDs and IONs, retinitis pigmentosa, accounting for almost half of IRDs, remains only partly molecularly defined

Assessing exposure to disinfection by-products in women of reproductive age living in Corpus Christi, Texas, and Cobb county, Georgia: descriptive results and methods.

We conducted a field study in Corpus Christi, Texas, and Cobb County, Georgia, to evaluate exposure measures for disinfection by-products, with special emphasis on trihalomethanes (THMs). Participants were mothers living in either geographic area who had given birth to healthy infants from June 1998 through May 1999. We assessed exposure by sampling blood and water and obtaining information about water use habits and tap water characteristics. Two 10-mL whole blood samples were collected from each participant before and immediately after her shower. Levels of individual THM species (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) were measured in whole blood [parts per trillion (pptr)] and in water samples (parts per billion). In the Corpus Christi water samples, brominated compounds accounted for 71% of the total THM concentration by weight; in Cobb County, chloroform accounted for 88%. Significant differences in blood THM levels were observed between study locations. For example, the median baseline blood level of bromoform was 0.3 pptr and 3.5 pptr for participants in Cobb County and Corpus Christi, respectively (p = 0.0001). Differences were most striking in blood obtained after showering. For bromoform, the median blood levels were 0.5 pptr and 17 pptr for participants in Cobb County and Corpus Christi, respectively (p = 0.0001). These results suggest that blood levels of THM species vary substantially across populations, depending on both water quality characteristics and water use activities. Such variation has important implications for epidemiologic studies of the potential health effects of disinfection by-products

High prevalence of PRPH2 in autosomal dominant retinitis pigmentosa in france and characterization of biochemical and clinical features.

PURPOSE: To assess the prevalence of PRPH2 in autosomal dominant retinitis pigmentosa (adRP), to report 6 novel mutations, to characterize the biochemical features of a recurrent novel mutation, and to study the clinical features of adRP patients. DESIGN: Retrospective clinical and molecular genetic study. METHODS: Clinical investigations included visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, and electroretinogram (ERG) recording. PRPH2 was screened by Sanger sequencing in a cohort of 310 French families with adRP. Peripherin-2 protein was produced in yeast and analyzed by Western blot. RESULTS: We identified 15 mutations, including 6 novel and 9 previously reported changes in 32 families, accounting for a prevalence of 10.3% in this adRP population. We showed that a new recurrent p.Leu254Gln mutation leads to protein aggregation, suggesting abnormal folding. The clinical severity of the disease in examined patients was moderate with 78% of the eyes having 1-0.5 of visual acuity and 52% of the eyes retaining more than 50% of the visual field. Some patients characteristically showed vitelliform deposits or macular involvement. In some families, pericentral RP or macular dystrophy were found in family members while widespread RP was present in other members of the same families. CONCLUSIONS: The mutations in PRPH2 account for 10.3% of adRP in the French population, which is higher than previously reported (0%-8%) This makes PRPH2 the second most frequent adRP gene after RHO in our series. PRPH2 mutations cause highly variable phenotypes and moderate forms of adRP, including mild cases, which could be underdiagnosed

Intimal aortic sarcoma mimicking ruptured thoracoabdominal type IV aneurysm. a rare case report and review of the literature

Primary intimal aortic sarcoma represents a very rare and highly lethal medical entity. Diagnosis is made either by embolic events caused by the tumor or by surrounding tissue symptoms such as pain. Herein we report an extremely rare case of a 51-year-old man previously operated for ascending aortic aneurysm, who presented with clinical and radiological findings suggestive of a ruptured thoracoabdominal type IV aneurysm. The patient underwent radical resection of the aorta and surrounding tissue with placement of a composite 4-branched graft. The diagnosis was made by frozen section and regular histopathologic examination of the specimen and the patient received adjuvant chemotherapy. Nine months after surgery the patient is still alive and has no signs of recurrence. We review the literature and discuss the option of postoperative chemotherapy