Variants detection in regions of segmental duplication facilitates molecular diagnosis for IEI such as chronic granulomatous disease caused by NCF1 mutations

With the expanding application of next-generation sequencing (NGS) in clinical practice, rapid progress has been made in molecular diagnoses for diseases such as inborn errors of immunity (IEI). However, due to characteristic short read length and fragment size for NGS, genomic regions with segmental duplication pose a big challenge for accurate mutation detection. Reads originating from segmental duplications are mapped with high ambiguity and are often discarded by most variant callers, leading to poor variant identification. Dozens of known IEI causal genes are located in regions of segmental duplications, such as NCF1, IGLL1, FCGR3A, etc. It is important to increase the sensitivity of mutation detections in such regions.