C.35delG/ GJB2 and del(GJB6-D13S1830) mutations in Croatians with prelingual non-syndromic hearing impairment.

BACKGROUND: C.35delG/GJB2 mutation is the most frequent genetic cause of deafness in Caucasians. Another frequent mutation in some Caucasian populations is del(GJB6-D13S1830). Both GJB2 and GJB6 genes belong to the same DFNB1 locus and when the two mutations are found in combination in a hearing-impaired person, a digenic pattern of inheritance is suggested. METHODS: We examined 63 Croatian subjects (25 familial and 38 sporadic cases) with prelingual non-syndromic hearing impairment by polymerase chain reaction for the presence of the c.35delG/GJB2 and the del(GJB6-D13S1830) mutations. RESULTS: Of the 63 unrelated hearing-impaired subjects, the mutation c.35delG/GJB2 was found in 21 subjects (33.3%). In 5 of them the mutation was found in the heterozygous state, all of them being compound heterozygotes, as sequencing revealed a second mutation within the coding region of the gene in 3 subjects, and a splice site mutation in 2 subjects. The del(GJB6-D13S1830) mutation was not found in the investigated hearing-impaired Croatian subjects. CONCLUSION: Our results contribute to the knowledge of geographic distribution and population genetics of the GJB2 and GJB6 mutations in the Europeans.

Recurrent venous thrombosis despite 'optimal anticoagulation therapy' for antiphospholipid syndrome--could new oral anticoagulants solve the problem?

The aim was to determine the validity of the international normalized ratio (INR) and prothrombin time (PT) as a monitor for warfarin therapy in patients with lupus anticoagulants and recurrent thrombosis, and to investigate alternative approaches to monitoring warfarin therapy and new treatment options in these patients. A case is described of a 63-year-old female with antiphospholipid syndrome and recurrent venous thrombosis despite optimal adjusted warfarin therapy. In patients with lupus anticoagulants, the INRs obtained while receiving warfarin vary and often overestimate the extent of anticoagulation, while PT without receiving warfarin is often prolonged. In conclusion, lupus anticoagulants can influence PT and lead to INR that does not accurately reflect the true level of anticoagulation. Optimizing of (warfarin) oral anticoagulation therapy could be achieved by individual monitoring of anticoagulation effect with a test thatis insensitive to lupus anticoagulants (chromogenic factor X assay). Emerging oral anticoagulants, direct thrombin inhibitors and direct factor Xa inhibitors, such as dabigatran and rivaroxaban, with a predictable anticoagulant response and little potential for food or drug interactions, have been designed to be administered in fixed doses without coagulation monitoring and could be the treatment choice for these patients.