Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome.

Thiamine-responsive megaloblastic anaemia syndrome (TRMA; MIM 249270) is an autosomal recessive disorder with features that include megaloblastic anaemia, mild thrombocytopenia and leucopenia, sensorineural deafness and diabetes mellitus. Treatment with pharmacologic doses of thiamine ameliorates the megaloblastic anaemia and diabetes mellitus. A defect in the plasma membrane transport of thiamine has been demonstrated in erythrocytes and cultured skin fibroblasts from TRMA patients. The gene causing TRMA was assigned to 1q23.2-q23.3 by linkage analysis. Here we report the cloning of a new gene, SLC19A2, identified from high-through-put genomic sequences due to homology with SLC19A1, encoding reduced folate carrier 1 (refs 8-10). We cloned the entire coding region by screening a human fetal brain cDNA library. SLC19A2 encodes a protein (of 497 aa) predicted to have 12 transmembrane domains. We identified 2 frameshift mutations in exon 2. a 1-bp insertion and a 2-bp deletion, among four Iranian families with TRMA. The sequence homology and predicted structure of SLC19A2, as well as its role in TRMA, suggest that its gene product is a thiamine carrier, the first to be identified in complex eukaryotes.     

A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy.

Malattia Leventinese (ML) and Doyne honeycomb retinal dystrophy (DHRD) refer to two autosomal dominant diseases characterized by yellow-white deposits known as drusen that accumulate beneath the retinal pigment epithelium (RPE). Both loci were mapped to chromosome 2p16-21 (refs 5,6) and this genetic interval has been subsequently narrowed. The importance of these diseases is due in large part to their close phenotypic similarity to age-related macular degeneration (AMD), a disorder with a strong genetic component that accounts for approximately 50% of registered blindness in the Western world. Just as in ML and DHRD, the early hallmark of AMD is the presence of drusen. Here we use a combination of positional and candidate gene methods to identify a single non-conservative mutation (Arg345Trp) in the gene EFEMP1 (for EGF-containing fibrillin-like extracellular matrix protein 1) in all families studied. This change was not present in 477 control individuals or in 494 patients with age-related macular degeneration. Identification of this mutation may aid in the development of an animal model for drusen, as well as in the identification of other genes involved in human macular degeneration.     

Activitéin vivo de dérivés de la thiourée contre le virus de l'influenza

Summary A large number of sulphur-containing compounds bearing the thiourea group -NH-CS-NH-, including substituted thiocarbanilides, 1-acyl-4-arylthiosemicar-bazides, 1-(arylaminothioformyl)-thiosemicarbazides, 4-aryl-1-(arylaminothioformyl)- thiosemicarbazides, and other related substances have been tested for potential antiviral activity. Several of these compounds have been found chemotherapeutically active against influenza virus.

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Communication présentée au Congrès international de Chimie pure et appliquée de Zürich (Juillet 1955).     

Alteration in the SAT-chromosome ofAllium cepa affecting the size of the nucleolus

Resumen Se describe el hallazgo de un bulbo deAllium cepa en el cual los dos nucleolos de cada nÚcleo muestran una clara diferencia de tamaño. El nucleolo menor posee aproximadamente la mitad del diámetro del nucleolo normal. Esta alteración de la morfología nucleolar se correlaciona con la ausencia de satélite en uno de los dos cromosomas normalmente satelizados.

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The work reported in this paper was undertaken during the tenure of a Research Training Fellowship awarded by the International Agency for Research on Cancer.