Genetic Dominant Variants in STUB1, Segregating in Families with SCA48, Display In Vitro Functional Impairments Indistinctive from Recessive Variants Associated with SCAR16.

Variants in STUB1 cause both autosomal recessive (SCAR16) and dominant (SCA48) spinocerebellar ataxia. Reports from 18 STUB1 variants causing SCA48 show that the clinical picture includes later-onset ataxia with a cerebellar cognitive affective syndrome and varying clinical overlap with SCAR16. However, little is known about the molecular properties of dominant STUB1 variants. Here, we describe three SCA48 families with novel, dominantly inherited STUB1 variants (p.Arg51_Ile53delinsProAla, p.Lys143_Trp147del, and p.Gly249Val). All the patients developed symptoms from 30 years of age or later, all had cerebellar atrophy, and 4 had cognitive/psychiatric phenotypes. Investigation of the structural and functional consequences of the recombinant C-terminus of HSC70-interacting protein (CHIP) variants was performed in vitro using ubiquitin ligase activity assay, circular dichroism assay and native polyacrylamide gel electrophoresis. These studies revealed that dominantly and recessively inherited STUB1 variants showed similar biochemical defects, including impaired ubiquitin ligase activity and altered oligomerization properties of the CHIP. Our findings expand the molecular understanding of SCA48 but also mean that assumptions concerning unaffected carriers of recessive STUB1 variants in SCAR16 families must be re-evaluated. More investigations are needed to verify the disease status of SCAR16 heterozygotes and elucidate the molecular relationship between SCA48 and SCAR16 diseases

Asbestos-Related Health Risks in Estonia

Asbestos has been declared a proven human carcinogen by the U.S. Environ-mental Protection Agency and by the International Agency for Research on Cancer of the World Health Organization. Since 1983, the European Union has enforced health protection directions in this field, which have been the basis for legal acts of Member States. The Estonian Republic is a country where asbestos and asbestos-containing materials have been used in quite large quantities, especially during the Soviet period. Today the use and sale of asbestos minerals and asbestos containing products are prohibited in Estonia. Unfortunately there has been no substantial overview of the health status of workers exposed to asbestos. The objective of this study was to evaluate the extent of health risks of workers exposed to asbestos in Estonia