Fig. 1.
RPSA heterozygous coding mutations are the most frequent genetic etiology of ICA. (A) Manhattan plot showing the p-value for tests of the hypothesis that “mutations in a given gene were not specific to the ICA cohort”. Each dot represents one gene. X axis: physical position of each gene on the chromosome. Y axis: −log10(p). p was calculated for Fisher’s exact test comparing 23 exomes from 23 ICA kindreds and 508 exomes from patients with phenotypes other than invasive bacterial disease. The gray dashed line indicates threshold for statistical significance (0.05/4,222=1.2×10−5) (B) Familial segregation of all RPSA coding mutations. Mutations are described in red. Capital letters represent the kindred code. When available, the genotype of RPSA is indicated under each symbol. WT, wild-type; M, mutant. Black, ICA; gray, probable ICA.