Characterization of a Factor H Mutation That Perturbs the Alternative Pathway of Complement in a Family with Membranoproliferative GN

Complement C3 activation is a characteristic finding in membranoproliferative GN (MPGN). This activation can be caused by immune complex deposition or an acquired or inherited defect in complement regulation. Deficiency of complement factor H has long been associated with MPGN. More recently, heterozygous genetic variants have been reported in sporadic cases of MPGN, although their functional significance has not been assessed. We describe a family with MPGN and acquired partial lipodystrophy. Although C3 nephritic factor was shown in family members with acquired partial lipodystrophy, it did not segregate with the renal phenotype. Genetic analysis revealed a novel heterozygous mutation in complement factor H (R83S) in addition to known risk polymorphisms carried by individuals with MPGN. Patients with MPGN had normal levels of factor H, and structural analysis of the mutant revealed only subtle alterations. However, functional analysis revealed profoundly reduced C3b binding, cofactor activity, and decay accelerating activity leading to loss of regulation of the alternative pathway. In summary, this family showed a confluence of common and rare functionally significant genetic risk factors causing disease. Data from our analysis of these factors highlight the role of the alternative pathway of complement in MPGN.     

A pilot study to validate measures of the theory of reasoned action for organ donation behavior

The present study aimed at taking the first attempt in validating the measures generated based on the theory of reasoned action (TRA). A total of 211 university students participated in the study, 95 were included in the exploratory factor analysis and 116 were included in the confirmatory factor analysis. The TRA measurements were established with adequate psychometric properties, internal consistency, and construct validity. Findings also suggested that attitude toward organ donation has both a cognitive and affective nature, while the subjective norm of the family seems to be important to students’ views on organ donation.