Population Carrier Rates of Pathogenic ARSA Gene Mutations: Is Metachromatic Leukodystrophy Underdiagnosed?

BACKGROUND: Metachromatic leukodystrophy (MLD) is a severe neurometabolic disease caused mainly by deficiency of arylsulfatase A encoded by the ARSA gene. Based on epidemiological surveys the incidence of MLD per 100,000 live births varied from 0.6 to 2.5. Our purpose was to estimate the birth prevalence of MLD in Poland by determining population frequency of the common pathogenic ARSA gene mutations and to compare this estimate with epidemiological data. METHODOLOGY: We studied two independently ascertained cohorts from the Polish background population (N∼3000 each) and determined carrier rates of common ARSA gene mutations: c.459+1G>A, p.P426L, p.I179S (cohort 1) and c.459+1G>A, p.I179S (cohort 2). PRINCIPAL FINDINGS: Taking into account ARSA gene mutation distribution among 60 Polish patients, the expected MLD birth prevalence in the general population (assuming no selection against homozygous fetuses) was estimated as 4.0/100,000 and 4.1/100,000, respectively for the 1(st) and the 2(nd) cohort with a pooled estimate of 4.1/100,000 (CI: 1.8-9.4) which was higher than the estimate of 0.38 per 100,000 live births based on diagnosed cases. The p.I179S mutation was relatively more prevalent among controls than patients (OR = 3.6, P = 0.0082, for a comparison of p.I179S frequency relative to c.459+1G>A between controls vs. patients). CONCLUSIONS/SIGNIFICANCE: The observed discrepancy between the measured incidence of metachromatic leukodystrophy and the predicted carriage rates suggests that MLD is substantially underdiagnosed in the Polish population. The underdiagnosis rate may be particularly high among patients with p.I179S mutation whose disease is characterized mainly by psychotic symptoms

Heads or tails—fish hatching

Background. Hatching is a process in which the embryo emerges from the egg by breaking the protective egg shell. Our preliminary observations indicate that hatching duration and time-distribution may vary among and within the fish species, and that some embryos fail to hatch or hatch incompletely, probably due to the “incorrect” hatching way. So the aim of this study was a detailed description of hatching of three fish species: common carp, barbel, and rainbow trout. Materials and methods. Three species of fish: common carp, Cyprinus carpio; barbel, Barbus barbus; and rainbow trout, Oncorhynchus mykiss; were examined for their hatching modes. The mode and the time of hatching of each larva were noted. Newly hatched larvae were counted and examined. The malformations were classified. Observations of embryos and larvae were done using the stereoscopic microscope Nikon connected to the computer with the MultiScan 8.4 image analysis system; the hatching embryos and larvae were photographed. Results. Three modes of hatching were observed, two of them similar in all three fish species. Some fish started hatching tail first from the egg shell, others head first or—specifically for barbel—yolk sac first. The data obtained in the present study showed that tail hatching was the most successful in all fish species, and shown by most good quality larvae. The majority of tail-hatched larvae developed normally and were viable, and only some of them were deformed and showed slight morphological defects, mainly single vertebral malformations that in most cases were negligible. Head hatching was the precarious in carp, and in all fish species less common and successful comparing to the tail hatching. Conclusion. The hatching mode could beused as another good parameter for estimation of quality of eggs and larvae

Sezonowe zmiany parametrów hematologicznych u młodocianych karpi w warunkach laboratoryjnych

Annual changes in hematological parameters of common carp juveniles under laboratory conditions. The aim of the study was to evaluate the changes of the values of hematological parameters of carp juveniles in annual cycle under stable laboratory conditions. Some parameters showed distinct rhythms of changes, e.g. 2 peaks of hematocrit occurred in II and VIII, of hemoglobin concentration in I and VI, while erythrocyte count showed maximum in II. The largest erythrocytes were observed in VIII, and the smallest in XII. Leukocyte count showed two peaks in XII and III. Maximum lymphocyte frequency occurred in III and minimum in XI, while percentage of neutrophils showed the reverse pattern. Oxidative metabolic activity of phagocytes peaked in III, while minimum occurred in XI–XII and VI–VII. Thrombocyte count was highest in XII, and lowest in VII. The obtained results revealed that the values of hematological parameters in carp considerably changed during the year despite little alterations in environmental factors. Some of these changes, e.g. increase in oxidative activity of phagocytes in spring and increase in hemoglobin level in summer were similar to those that occur in fi sh under natural conditions. Another changes, such as increase in erythrocyte size or decrease in leukocyte count suggest long-term adjustment to the laboratory environment

Effect of genotype, environment and their interaction on quality parameters of wheat breeding lines of diverse grain hardness

Understanding the contribution of genotype, environment and genotype-by-environment interaction to wheat grain quality facilitates the selection for quality in breeding programs. Stability of grain quality characteristics is an important requirement in the baking industry. We assessed 24 winter wheat genotypes with different grain hardness in multienvironment trials at four locations and two levels of fertilization in each location. Grain samples were analyzed for hardness, protein and starch content, and wet gluten content, Zeleny sedimentation value, alveograph parameter (W) and hectoliter weight. All parameters were evaluated on whole grains using the near infrared transmittance technique. Differences between hard and soft genotypes appeared to be significant, apart from grain hardness, for protein content, Zeleny test and alveograph parameter. Genotype was found to have a major influence only on grain hardness; for protein content, wet gluten and Zeleny sedimentation value environment prevailed the influence of genotype, and for starch content, alveograph W parameter and hectoliter weight both sources of variation had similar importance. Genotype-by-environment interaction was of smaller size relative to genotype and environment in terms of all the studied quality parameters. Stable genotypes predominate the breeding lines studied. Response of unstable genotypes to environmental conditions was nonlinear in most cases

Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy

We report on a 36-year-old man with cerebellar-extrapyramidal syndrome and severe heart failure because of dilated cardiomyopathy of unknown origin. Dysarthria and cardiac arrhythmia began at early childhood (4 years of age). Brain MRI (28 years of age) demonstrated severe cerebellar atrophy. At the age 32, he presented with dysarthria, ataxia, dystonia, and tremor of the right hand, bilateral slowed neural conduction in the visual pathways, and decreased mental acuity. At the age of 33 years, the patient underwent cardiac transplantation because of severe dilated cardiomyopathy. In the TPP1 gene, biallelic variants were identified: previously reported p.(Leu13Pro) and novel p.(Tyr508Cys) variant. Additionally, hemizygous novel missense variant in the ABCD1 gene was inherited from the mother p.(Arg17His). Normal very-long-chain fatty acids (VLCFA) levels both in patient and his mother excluded ABCD1 mutation as the pathogenic one. Tripeptidyl peptidase 1 (TPP1) activity was reduced (8,8 U/mg protein/h; reference range: 47.4 ± 10.7). In light microscopy the biopsy specimens obtained from explanted heart showed severe myocyte hypertrophy with perinuclear vacuolization with inclusions. Electron microscopy revealed absence of lipofuscin accumulation, no ultrastructural curvilinear profiles, fingerprint bodies, or granular osmiophilic deposits (GRODs) in lysosomes. As described here, the patient presents clinical symptoms observed in benign forms of ceroid lipofuscinosis type 2 (CLN2) and simultaneously some features of autosomal recessive spinocerebellar ataxia type 7 (SCAR7), which is also caused by mutations in the TPP1 gene