XXXX Due to @entity1659 in Serbia: Two Novel Mutations and Evidence of Genotype-Phenotype Association.

@entity1659 @entity1 @entity72249 @entity4 @entity19459 @entity534 @entity74 @entity490 @entity72250 @entity7058 @entity38524 @entity72248
UNASSIGNED: @entity1659 due to C1 inhibitor deficiency (C1- @entity19459 - @entity7058 ) is a rare @entity74 characterized by recurrent life-threatening @entity4 and/or @entity490 and caused by mutations affecting the C1 inhibitor gene, @entity19459 . We sought to investigate the spectrum of @entity19459 mutations in Serbia and the possible genotype-phenotype association. C1- @entity19459 - @entity7058 was diagnosed on the basis of clinical and laboratory criteria in 40 @entity1 from 27 families; four were asymptomatic. Mutational analysis of the @entity19459 gene was performed by sequencing and multiplex ligation-dependent probe amplification. Disease-causing mutations in @entity19459 were identified in all @entity1 . In C1- @entity19459 - @entity7058 type I, we identified 19 different mutations, including 6 missense mutations, 6 nonsense mutations, 2 small deletions, 1 small insertion, 2 splicing defects and 2 large deletions. Two of the mutations ( @entity72248 and @entity72249 ) are reported here for the first time. All C1- @entity19459 - @entity7058 type II @entity1 from three families harboured the same substitution ( @entity72250 ). Based on the type of mutation identified in the @entity19459 gene, @entity1 were divided into two groups: group 1 (nonsense, frameshift, large deletions/insertions, splicing defect, and mutations at @entity534 444) or group 2 (missense, excluding mutations at Arg444). Significant differences were found in the clinical severity score (P = 0.005), prevalence of laryngeal (P = 0.040) and facial (P = 0.013) @entity4 , and long-term prophylaxis (P = 0.023) between the groups with different types of mutations. Because our population consisted of related subjects, differences in the severity score between mutation groups were further confirmed using the generalized estimating equation (P = 0.038). Our study identified 20 different disease-causing mutations, including two novel mutations, in all C1- @entity19459 - @entity7058 @entity1 , highlighting the heterogeneity of mutations in the @entity19459 gene. Furthermore, it appears that mutations with a clear effect on @entity38524 function might be responsible for a more severe disease phenotype.
