Hereditary isolated renal magnesium loss maps to chromosome 11q23.

Hypomagnesemia due to isolated renal magnesium loss has previously been demonstrated in two presumably unrelated Dutch families with autosomal dominant mode of inheritance. Patients with magnesium deficiency may suffer from tetany and convulsions, but the patients with hereditary renal magnesium wasting can also be clinically nonsymptomatic. In a genomewide linkage study, we first excluded a possible candidate region, on chromosome 9q, that encompasses the gene for intestinal hypomagnesemia with secondary hypocalcemia and, subsequently, found linkage to markers on chromosome 11q23. Detailed haplotype analyses identified a common haplotype segregating in both families, suggesting both their relationship through a common ancestor and the existence of a single, hypomagnesemia-causing mutation within them. The maximum two-point LOD score (Zmax) was found for marker D11S4127 (Zmax=6.41 at a recombination fraction of. 00), whereas a multipoint analysis gave a Zmax of 8.24 between markers D11S4142 and D11S4171. Key recombination events define a 5. 6-cM region between these two markers on chromosome 11q23. We conclude that this region encompasses a gene, involved in renal magnesium handling, that is mutated in our patients and is different from the gene involved in intestinal magnesium handling.     

Antioxidant effect and polyphenol content of Syringodium filiforme (Cymodoceaceae)

The marine phanerogam Syringodium filiforme, known as "manatee grass", is a common species that grows in coastal areas associated to Thalassia testudinum. With the aim to describe some of its possible chemical characteristics, this study was performed with a sample of 1.2 kg, collected in March 2009, in Guanabo beach, Havana, Cuba. The sample was dried (less than 12% humidity) and a total extract prepared; other three extracts were prepared with the use of solvents of increasing polarity. The phytochemical screening and analytical determinations of each fraction were undertaken Total polyphenol content was determined using pyrogallol as reference's standard; chlorophyll a and b and anthocyanin content were also quantified. Total extract and fractions antioxidant activity were evaluated by using the free radical scavenging activity assay with 1,1-Diphenyl-2-Picrylhydrazyl reactive (knowing as DPPH's method). The phytochemical screening of the different extracts detected the presence of high concentrations of flavonoids, phenols, terpenes, antocyanins, reducing sugars and alkaloids. The total extract and methanol fraction showed significant free radical scavenging properties, while the petroleum ether fraction showed moderate activity, and the chloroform fraction and the aqueous soluble precipitate (residual salt) obtained didn't show antioxidant properties against free radicals. The results of this work confirmed the potentialities of this species for biological purposes.     

Hereditary angioedema

Summary 3 families with hereditary angioedema in 9 members are described. The serum concentrations of complement factors C3, C4, and C-inhibitor (CINH) were determined in all available family members. C inhibiting activity was characteristically low or absent in sera from patients. CINH and C4 concentrations were also low, whereas C3 was present in normal concentrations in patients and in unaffected family members. In all 3 families fatal attacks of laryngeal edema had occured. 4 individuals, 2 children and 2 adults, had low concentrations of CINH and C4 but had never experienced symptoms of angioedema.

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Zusammenfassung 3 Familien mit hereditärem Angioödem bei insgesamt 9 Mitgliedern werden beschrieben. Die Serumkonzentrationen der Komplementfaktoren C3, C4 und des C-Inhibitors (CINH) wurden bei allen erreichbaren Familienmitgliedern bestimmt. Die C-Hemmaktivität und die Konzentrationen von CINH und C4 waren in den Patientenseren niedrig. Der C3-Serumspiegel war jedoch bei Patienten und gesunden Familienmitgliedern normal. In allen 3 Familien sind tödlich verlaufende Anfälle von Larynxödem vorgekommen. 4 Familienmitglieder, 2 Kinder und 2 Erwachsene, waren trotz niedriger Serumkonzentrationen von C4 und CINH asymptomatisch.

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Supported in part by Deutsche Forschungsgemeinschaft.     

Hereditary hemochromatosis

The advent of the genetics era has profoundly changed the way we look at iron related diseases, particularly hemochromatosis. New discoveries have challenged historical concepts about the disease, such as its monogenic nature, intestinal origin or complete phenotypic penetrance. This review presents a new concept of hemochromatosis which stems from the idea that, beyond their genetic diversities, all known hemochromatoses have in common the same metabolic abnormality: the genetically determined failure to prevent unneeded iron from entering the circulatory pool. Inappropriate levels of hepcidin, the iron hormone, appear now as the central pathogenic event in all forms of hemochromatosis: depending on the protein involved, and its effect on hepatic production of hepcidin, the phenotype varies, ranging from massive early-onset iron loading with severe organ disease (e.g., associated with homozygous mutations of hemojuvelin or hepcidin itself) to the milder late-onset phenotype characterizing the classic and highly prevalent HFE-related form or the rare transferrin receptor 2-related form. In vitro and in vivo studies will be needed to dissect the consequences of each hereditary hemochromatosis allele and increase our understanding of the precise contribution of each gene to the hereditary hemochromatosis phenotype.     

Hereditary damage

Summary For the purposes of radiation protection, risk estimates should be based on effects of irradiation at low doses and low dose-rates. Although few genetic studies have been made on effects at low doses those carried out at low dose-rates suggest that the response is generally linear for induction of both gene mutations and chromosome aberrations. For obtaining an overall genetic risk assessment under these conditions a doubling dose of 100 rem (1 Sv) has been used by the ICRP and other bodies, with respect to radiation of low LET. In addition, it is necessary to know frequencies of human hereditary conditions, the extent to which these frequencies are maintained by recurrent mutation and the average number of generations the different categories of hereditary damage persist in the population. By the use of this information, as well as some data on translocation induction obtained directly from human exposures, an estimate of the risk of serious hereditary ill health in the first two generations after low-level radiation exposure was obtained for the Commission by one of its task groups. Thus the estimate of 10^–2 Sv^–1 used in ICRP 26 has a factual basis, although a number of far-reaching assumptions have still to be made when any risk estimation of this nature is attempted.Invited paper, presented at the 14th Annual Meeting of European Society of Radiation Biology, Jülich, Germany, October 8–14, 1978