Discovery of novel alleles in Kartagener's syndrome.

Whole exome sequencing of a Turkish cohort of 17 adult Kartagener's syndrome patients with situs inversus yielded a high diagnostic yield.

• The cohort comprised 17 adult patients, all with situs inversus.
• Variants were prioritised on sequencing quality, population allele frequency, and predicted functional impact.
• Analysis covered single-nucleotide variants, small insertions/deletions, and copy-number variations.
• Restricting the cohort to patients with situs inversus gave a phenotype-specific context, making genes unrelated to left-right axis determination less likely to explain disease.

Pathogenic or potentially disease-associated variants were found in multiple established PCD genes.

• Genes with variants included DNAH5, DNAI1, DNAI2, DNAAF1, DNAAF3, CFAP300, and ODAD1.
• Several of the detected alleles were novel.
• This expanded the variant spectrum associated with Kartagener's syndrome.

In one patient lacking biallelic variants in known PCD genes, expanded analysis identified heterozygous variants in DLEC1 and DNAAF9 plus a hemizygous copy number loss in EZR.

• DLEC1 and DNAAF9 are cilia-associated genes.
• EZR is a gene known to affect motile cilia function.
• The authors state that the possible relevance of these concurrent findings warrants further investigation in genetically unresolved cases.

The study supports phenotype-driven genomic analysis in genetically heterogeneous ciliopathies.

• KS accounts for approximately 50% of PCD cases, and up to 30% of PCD cases remain genetically unresolved.
• Studies focused specifically on KS cohorts remain limited.
• Analysis of this KS-specific cohort demonstrated a high diagnostic yield.