A novel mutation W388X underlying properdin deficiency in a Finnish family.

Properdin deficiency is a rare immunological disorder inherited as an X-chromosomal recessive trait. Properdin deficiency poses a significant risk for severe meningococcal infections. About 20 mutations have been reported to underlie properdin deficiency. Here we report a large Finnish family with a novel mutation in the properdin gene (CFP). Based on the total absence of properdin activity in a 14-year-old male patient with an infection resembling meningococcal bacteraemia, the coding region and splice sites of the gene were sequenced. The mutation is located in exon 9 and changes guanine to adenine at nucleotide 1164 (c.1164G>A) that causes tryptophan to change to a premature stop codon (W388X). The mother of the patient was shown to be a carrier of the mutation. In total, the mutation was identified in six females and three young males in the family. The mutation must be inherited from the grandfather who had died of an unknown infectious disease. This is the first mutation of the properdin gene identified in Finland.

Complement factor H variant Y402H is not a risk factor for preeclampsia in the Finnish population.

OBJECTIVE: Variations in complement factor H, which down-regulates the activity of the alternative complement pathway, have been associated with different vascular disorders. Here we examine whether factor H variation is involved in the etiology of preeclampsia. METHODS: We studied 110 women with preeclampsia and 99 controls for complement factor H variations by sequencing. RESULTS: No significant differences in the genotype or allele frequencies of the Y402H variant were detected between the two groups. No sequence variations were detected in the short consensus repeat domain 20 of the gene. CONCLUSIONS: Neither the Y402H variant, nor mutations in the short consensus repeat domain 20 of the gene is associated with preeclampsia. For examination of possible links to other polymorphisms or detection of small genotypic effects, studies in larger sample sets are warranted.

The effect of complement factor H Y402H polymorphism on the outcome of photodynamic therapy in age-related macular degeneration.

PURPOSE: Photodynamic therapy (PDT) has been widely used in the treatment of age-related macular degeneration (AMD). The complement cascade has an important role in the tissue reactions occurring after PDT. The Y402H polymorphism of the complement factor H (CFH) gene has been identified as a risk factor for AMD. Since CFH is central in the regulation of the complement system the authors wanted to analyze whether the CFH Y402H polymorphism modifies the PDT outcome in AMD. METHODS: A total of 88 patients having been treated with PDT and without further scheduled PDT sessions were analyzed. Depending on the situation at their final PDT session the patients were classified retrospectively as PDT-responders or PDT-nonresponders. All patients were genotyped for the CFH Y402H polymorphism. RESULTS: The proportion of PDT-responders was 18/26 (69.2%) in patients homozygous for the CFH Y402H risk allele, 34/50 (68.0%) in heterozygous, and 7/12 (58.3%) in patients with the normal genotype (p=0.520). The median number of PDT treatments of the PDT-responders was three for all the genotypes. CONCLUSIONS: The dysfunction of the CFH related to the risk of AMD and caused by the Y402H polymorphism does not modify the outcome of PDT. Genotyping for CFH Y402H cannot be used to select patients for this treatment.