Preliminary Results of Whole Exome Sequencing in Turkish Primary Ciliary Dyskinesia Patients - Hacettepe University Experience: “Three candidate genes, five novel and two known mutations”

Abstract

Aim: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous trait and nearly 32 genes associated with this disease thus far. Recent technologies can detect approximately 60% of biallelic PCD mutations.However, whole-exome sequencing(WES) provides the opportunity for the (Genetically) undiagnosed PCD patients and describe both candidate genes and novel mutations. Here we aimed to reveal the underlying genetic risk variants of PCD patients with WES. Methods: WES was performed in 10 individuals with a history of PCD and who had a sibling with the diagnosis of PCD. Allele frequency and in-house database information with homozygosity approach was used for variant filtering. Lung Diseases NGS Panel which contains 180 known and candidate genes was also utilised. Results: Bioinformatic analysis ended up with 10 different homozygous variants which include INDEL, missense and nonsense alterations in both known and candidate PCD genes. Mutation analysis showed all affected siblings are homozygous for indicated variants. Variants identified by whole exome sequencing were also confirmed and the inheritence in families showed by Sanger sequencing. We detected novel and previously reported mutations in CCDC40, CCNO, DNAH5, DNAH9 and RSPH4A which are related to PCD. Our findings also suggest three candidate genes that were not reported in PCD patients so far. Conclusion: Diagnosis of patients with the detection of both disease associated and novel mutations is an important approach. These findings will guide to genotype-phenotype correlation and population based genetic studies of Turkish PCD patients in future.