Thyroid and Breast Cancer in 2 Sisters With Monoallelic Mutations in the Ataxia Telangiectasia Mutated (ATM) Gene.

The presence of a bidirectional risk for metachronous carcinomas among women with thyroid and breast cancer is well established. However, the underlying risk factors remain poorly understood. Two sisters developed papillary thyroid cancer (PTC) at age 32 and 34 years, followed by ductal carcinoma of the breast at 44 and 42 years. The 2 children of the younger sister developed ataxia-telangiectasia; the son also developed lymphoblastic lymphoma and his sister died secondary to acute lymphoblastic leukemia (ALL). They were found to be compound heterozygous for ataxia telangiectasia mutated (ATM) gene mutations (c.3848T>C, p.L1283P; and c.802C>T, p.Q268X). Exome sequencing of the 2 sisters (mother and aunt of the children with ataxia-telangiectasia) led to the detection of the pathogenic monoallelic ATM mutation in both of them (c.3848T>C; minor allele frequency [MAF] < 0.01) but detected no other variants known to confer a risk for PTC or breast cancer. The findings suggest that monoallelic ATM mutations, presumably in conjunction with additional genetic and/or nongenetic factors, can confer a risk for developing PTC and breast cancer.

Pendrin and anoctamin as mediators of apical iodide efflux in thyroid cells.

PURPOSE OF REVIEW: Thyroid hormones are essential for normal development, growth, and metabolism. Their synthesis occurs in thyroid follicles and requires an adequate iodide supply and a sequence of regulated biochemical steps. The uptake of iodide into thyrocytes is well characterized, but its efflux at the apical membrane is poorly understood. This review discusses potential mechanisms underlying iodide efflux with emphasis on recent developments and controversies. RECENT FINDINGS: The functional characterization of pendrin (PDS/SLC26A4), a multifunctional anion exchanger, suggested that it could be involved in mediating iodide efflux. This is supported by the phenotype of patients with Pendred syndrome (deafness, goiter, partial iodide organification defect), which is caused by biallelic mutations in the SLC26A4 gene, as well as functional studies. However, apical iodide efflux is also possible in the absence of pendrin, implicating the presence of at least another channel. Recently, Anoctamin 1 (TMEM16A), a calcium-activated anion channel has been identified at the apical membrane of thyrocytes and functional studies suggest that it may play a predominant role in mediating iodide efflux. SUMMARY: Anoctamin and pendrin are two plausible candidates as mediators of apical iodide efflux. Their relative affinity for iodide and their exact physiological role await, however, further characterization.

Adherence and experimental infection of bacteria associated with periodontal infections of young cattle in Brazil ("Cara inchada")

In vitro- and in vivo-assays were conducted, to study the possible role of streptomycin- and actinomycin-producing soil actinomycetes for the pathogenesis of "Cara inchada" in cattle (CI). Adherence of Bacteroides spp. to epithelial cells of the bovine gingiva, known to be associated with the progressive lesions of CI, was significantly increased by the addition of streptomycin, actinomycin or antibiotic culture supernatants of the soil actinomycetes. Applications of these mixtures together with Actinomyces pyogenes to the marginal gingiva of the upper premolar teeth of about 1 month old Holstein Friesian calves did not lead to progressive lesions of CI. Only one calf exhibited a slight diarrhea and a temporary retraction of the gingiva at the site of application