Familial hypomagnesemia with secondary hypocalcemia (OMIM 602014) is an autosomal recessive disease that results in electrolyte abnormalities shortly after birth. Affected individuals show severe hypomagnesemia and hypocalcemia, which lead to seizures and tetany. The disorder has been thought to be caused by a defect in the intestinal absorption of magnesium, rather than by abnormal renal loss of magnesium. Restoring the concentrations of serum magnesium to normal values by high-dose magnesium supplementation can overcome the apparent defect in magnesium absorption and in serum concentrations of calcium. Life-long magnesium supplementation is required to overcome the defect in magnesium handling by these individuals. We previously mapped the gene locus to chromosome 9q in three large inbred kindreds from Israel. Here we report that mutation of TRPM6 causes hypomagnesemia with secondary hypocalcemia and show that individuals carrying mutations in this gene have abnormal renal magnesium excretion.

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Petunia hybrida is one of the classical subjects of investigation in plants in which the pathway of anthocyanin biosynthesis has been analysed genetically and biochemically. In petunia cyanidin- and delphinidin-derivatives, but no pelargonidin-derivatives are produced as pigments. This is due to the substrate specificity of the dihydroflavonol 4-reductase of petunia, which cannot reduce dihydrokaempferol. The petunia mutant RL01, which accumulates dihydrokaempferol, shows no flower pigmentation. RL01 served as a recipient for the transfer of the A1 gene of Zea mays encoding dihydroquercetin 4-reductase, which can reduce dihydrokaempferol and thereby provided the intermediate for pelargonidin biosynthesis. Transformation of RL01 with a vector p35A1, containing the A1-complementary DNA behind the 35S promotor leads to red flowers of the pelargonidin-type. Thus a new flower pigmentation pathway has been established in these plants.

The International Registry of Werner syndrome (www.wernersyndrome.org) has been providing molecular diagnosis of the Werner syndrome (WS) for the past decade. The present communication summarizes, from among 99 WS subjects, the spectrum of 50 distinct mutations discovered by our group and by others since the WRN gene (also called RECQL2 or REQ3) was first cloned in 1996; 25 of these have not previously been published. All WRN mutations reported thus far have resulted in the elimination of the nuclear localization signal at the C-terminus of the protein, precluding functional interactions in the nucleus; thus, all could be classified as null mutations. We now report two new mutations in the N-terminus that result in instability of the WRN protein. Clinical data confirm that the most penetrant phenotype is bilateral ocular cataracts. Other cardinal signs were seen in more than 95% of the cases. The median age of death, previously reported to be in the range of 46-48 years, is 54 years. Lymphoblastoid cell lines (LCLs) have been cryopreserved from the majority of our index cases, including material from nuclear pedigrees. These, as well as inducible and complemented hTERT (catalytic subunit of human telomerase) immortalized skin fibroblast cell lines are available to qualified investigators.

Homology-dependent gene silencing phenomena in plants have received considerable attention, especially when it was discovered that the presence of homologous sequences not only affected the stability of transgene expression, but that the activity of endogenous genes could be altered after insertion of homologous transgenes into the genome. Homology-mediated inactivation most likely comprises at least two different molecular mechanisms that induce gene silencing at the transcriptional or posttranscriptional level, respectively. In this review we discuss different mechanistic models for plant-specific inactivation mechanisms and their relationship with repeat-specific silencing phenomena in other species.