Figure 1.

CLPB variants in SCN. Flow diagrams summarizing independent sequencing results from the SCNIR (A) and French SCN registry (B-C). The number of cases carrying a specific variant is shown in parentheses. (D) Pedigrees for 2 de novo cases with available family studies. Parental and patient variant status was confirmed using Sanger sequencing. WT indicates that the relevant CLPB variant was not present. Male (square) and female (circle) family members are depicted as unaffected (white) or affected (black). Parentage for cases Fr-0019 and Fr-0038 was confirmed using short tandem repeat analysis. (E) Mutational spectrum of CLPB as identified in this series (top) vs previously reported biallelic variants (bottom). The overall domain architecture of human CLPB is shown and includes the mitochondrial localization sequence (MLS), ankyrin-rich repeats (ANK), ATPase domain, and C-terminal domain (CTD). (F) CLPB protein structure model based on data from the crystal structure of T thermophilus CLPB (PDB ID: 1qvr). Side chains are shown for the 5 mutated residues, found in 10 patients, that cluster around the ATP-binding pocket. *One patient was identified initially through clinical sequencing but subsequently enrolled in the SCNIR and underwent exome sequencing. Cyclic, cyclic neutropenia.