Identification of a Novel Variant in a Patient with Primary Ciliary Dyskinesia.

Background: encodes a protein with 1012 amino acids, which is a component of basal bodies and centrioles, essential for cilia biogenesis. was reported to be associated with X-chromosome linked dysmorphology syndrome in early studies and recent studies reported a few cases with primary ciliary dyskinesia (PCD) caused by deficiency.

Case Presentation: We report a 31-year-old man who suffered from recurrent respiratory infections with typical manifestations of primary ciliary dyskinesia. In addition to respiratory manifestations, the patient also had situs inversus, obesity, gastroesophageal reflux, and hearing impairment. Clubbing fingers and mild streblomicrodactyly were also observed.

Examination Result: We performed whole-exome sequencing to identify a novel variant c.2795delA:p.(Lys932Argfs*3) in . The hemizygous variant was predicted to be likely pathogenic by bioinformatic analysis software and ACMG guideline. High-speed video microscopy (HSVM), transmission electron microscopy (TEM), and immunofluorescence were performed to analyze the respiratory cilia. A high beating frequency and a stiff beating pattern were observed under HSVM, while there were no significant abnormalities in TEM and immunofluorescence. The sperm flagella examinations were also generally normal.

Conclusion: Our study identified a novel frameshift variant in causing PCD, enriched the genetic spectrum of variants, and verified that mutation can lead to only a PCD characteristic phenotype, while other -associated syndromic symptoms such as dysmorphic features and renal symptoms were not present.