Identification of compound heterozygous DNAH11 variants in a Han-Chinese family with primary ciliary dyskinesia.

Abstract

Primary ciliary dyskinesia (PCD) is a group of genetically and clinically heterogeneous disorders with motile cilia dysfunction. It is clinically characterized by oto‐sino‐pulmonary diseases and subfertility, and half of the patients have situs inversus (Kartagener syndrome). To identify the genetic cause in a Han‐Chinese pedigree, whole‐exome sequencing was conducted in the 37‐year‐old proband, and then, Sanger sequencing was performed on available family members. Minigene splicing assay was applied to verify the impact of the splice‐site variant. Compound heterozygous variants including a splice‐site variant (c.1974‐1G>C, rs1359107415) and a missense variant (c.7787G>A, p.(Arg2596Gln), rs780492669), in the dynein axonemal heavy chain 11 gene (DNAH11) were identified and confirmed as the disease‐associated variants of this lineage. The minigene expression in vitro revealed that the c.1974‐1G>C variant could cause skipping over exon 12, predicted to result in a truncated protein. This discovery may enlarge the DNAH11 variant spectrum of PCD, promote accurate genetic counselling and contribute to PCD diagnosis.