Identification of compound heterozygous DNAH11 variants in a Han-Chinese family with primary ciliary dyskinesia.
Ying XiongHong XiaLamei YuanSheng DengZerui DingHao DengPublished in: Journal of cellular and molecular medicine (2021)
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.
Keyphrases
- copy number
- genome wide
- single cell
- end stage renal disease
- high throughput
- ejection fraction
- poor prognosis
- newly diagnosed
- early onset
- oxidative stress
- small molecule
- peritoneal dialysis
- dna methylation
- prognostic factors
- hepatitis c virus
- genome wide identification
- mass spectrometry
- men who have sex with men
- case report