The RSPH4A Gene in Primary Ciliary Dyskinesia.

The radial spoke head protein 4 homolog A () gene is one of more than 50 genes that cause Primary ciliary dyskinesia (PCD), a rare genetic ciliopathy. Genetic mutations in the gene alter an important protein structure involved in ciliary pathogenesis. Radial spoke proteins, such as RSPH4A, have been conserved across multiple species. In humans, ciliary function deficiency caused by pathogenic variants results in a clinical phenotype characterized by recurrent oto-sino-pulmonary infections. More than 30 pathogenic genetic variants have been associated with PCD. In Puerto Rican Hispanics, a founder mutation ( (c.921+3_921+6delAAGT (intronic)) has been described. The spectrum of the PCD phenotype does not include laterality defects, which results in a challenging diagnosis. PCD diagnostic tools can combine transmission electron microscopy (TEM), nasal nitric oxide (nNO), High-Speed Video microscopy Analysis (HSVA), and immunofluorescence. The purpose of this review article is to provide a comprehensive overview of current knowledge about the gene in PCD, ranging from basic science to human clinical phenotype.