Identification of two novel dnaaf2 variants in two consanguineous families with primary ciliary dyskinesia

Abstract

Background: Dynein axonemal assembly factor 2 (DNAAF2) is involved in the early preassembly of dynein in the cytoplasm, which is essential for motile cilia function. Primary ciliary dyskinesia (PCD) associated with DNAAF2 variants has rarely been reported in females with infertility. Moreover, there is no report linking DNAAF2 to scoliosis in human. Materials and Methods: We recruited patients from two consanguineous families with a clinical diagnosis of PCD and collected their clinical history, laboratory tests, and radio-graphic data. Sequencing and bioinformatics analysis were then performed. Immunofluorescence and high-speed microscope analysis were used to support the patho-genicity of the variant. Results: Proband 1, a 26-year-old female from family I, exhibited scoliosis, bronchiectasis, sinusitis, situs inversus, and infertility. We found a novel homozygous missense variant in DNAAF2, c.491T>C, p.(Leu164Pro) in this patient. Subsequent immunofluorescence indi-cated the absence of outer dynein arm and inner dynein arm of cilia, and high-speed microscopy analysis showed that the most of the cilia are static, which support the patho-genicity of this variant. Proband 2, a 53-year-old female, presented with bronchiectasis, sinusitis, and infertility. In this patient, a new homozygous frameshift variant DNAAF2, c.822del, p.(Ala275Profs*10) was identified. The disease-causing variants mentioned above are not included in the current authorized genetic databases. Conclusion: Our findings expand the spectrum of DNAAF2 variants and link DNAAF2 to female infertility and likely scoliosis in patients with PCD.