DNAH11related

DNAH11-related refers to disorders caused by pathogenic variants in the DNAH11 gene, which encodes axonemal dynein heavy chain 11. This protein is a component of the outer dynein arm of motile cilia and flagella, and it plays a key role in generating the ciliary beat that propels mucus and fluids across epithelial surfaces. DNAH11 is expressed in tissues with motile cilia, including the respiratory tract, reproductive system, and brain ventricular system.

Genetically, DNAH11-related conditions are typically inherited in an autosomal recessive manner. A wide range of variants have been described, including missense, nonsense, frameshift, and splice-site changes. Genetic testing for primary ciliary dyskinesia (PCD) often uses targeted sequencing panels, but whole-exome sequencing can detect DNAH11 mutations when a wider differential is considered. Diagnostic yield varies, and confirmation may rely on functional assessment of ciliary motion and, in some cases, ciliary ultrastructure.

Clinically, DNAH11-related PCD presents with features common to motile ciliary defects: chronic year-round cough, recurrent sinopulmonary infections, chronic otitis media with effusion, and bronchiectasis. A subset of individuals may have laterality defects such as situs inversus totalis or heterotaxy. Male infertility due to impaired sperm motility can occur, and some newborns experience respiratory distress. Electron microscopy may show outer dynein arm defects, but DNAH11 mutations can also be associated with normal ultrastructure in certain cases.

Management is supportive and multidisciplinary, focusing on airway clearance, prompt treatment of infections, and surveillance for bronchiectasis. Fertility considerations and assisted reproductive options may be discussed for affected individuals. Currently, there is no cure for DNAH11-related conditions, but early diagnosis and care can improve quality of life and outcomes.