CFAP300, also known as C11orf70, is a gene encoding a protein that plays a crucial role in the assembly of ciliary dynein arms [2,8]. Motile cilia, hair-like organelles, rely on these dynein arms for their proper function. The malfunction of motile cilia due to CFAP300-related issues can lead to primary ciliary dyskinesia (PCD), a rare genetic condition [1,2,3,4,5,6,7].

Mutations in CFAP300 have been identified in patients with PCD from various populations, such as Finland, Slavic, Chinese, Russian, and Cypriot populations [1,2,3,6,7]. These mutations, like c.198_200delinsCC, c.466G>T, and c.95_103delGCCGGCTCC, result in a lack of the protein product or abnormal localization of dynein arm markers, leading to immotile airway epithelial cilia and missing dynein arms in ciliary axonemes [1,2,3]. In model organisms like the flatworm Schmidtea mediterranea, gene silencing experiments suggest a conserved role of CFAP300 in ciliary function [2]. In Paramecium, RNAi knockdown of the orthologous gene leads to combined loss of ciliary inner and outer dynein arms, reduced cilia beating, and swim velocity [8].

In conclusion, CFAP300 is essential for the assembly of dynein arms in motile cilia. Studies on CFAP300, including those using gene-silencing in model organisms, have enhanced our understanding of its role in PCD. These findings are valuable for improving the diagnosis of PCD in different populations and for guiding genetic counseling for affected individuals and their families [1,2,9].

References:

1. Schultz, Rüdiger, Elenius, Varpu, Fassad, Mahmoud R, Mitchison, Hannah M, Sironen, Anu I. 2022. CFAP300 mutation causing primary ciliary dyskinesia in Finland. In Frontiers in genetics, 13, 985227. doi:10.3389/fgene.2022.985227. https://pubmed.ncbi.nlm.nih.gov/36246608/

2. Zietkiewicz, Ewa, Bukowy-Bieryllo, Zuzanna, Rabiasz, Alicja, Rasteiro, Margarida, Witt, Michal. . CFAP300: Mutations in Slavic Patients with Primary Ciliary Dyskinesia and a Role in Ciliary Dynein Arms Trafficking. In American journal of respiratory cell and molecular biology, 61, 440-449. doi:10.1165/rcmb.2018-0260OC. https://pubmed.ncbi.nlm.nih.gov/30916986/

3. Zhou, Zheng, Qi, Qi, Wang, Wen-Hua, Ma, Jin-Zhao, Yao, Bing. 2024. A novel homozygous mutation of CFAP300 identified in a Chinese patient with primary ciliary dyskinesia and infertility. In Asian journal of andrology, 27, 113-119. doi:10.4103/aja202477. https://pubmed.ncbi.nlm.nih.gov/39254424/

4. Bolkier, Yoav, Barel, Ortal, Marek-Yagel, Dina, Vivante, Asaf, Pode-Shakked, Ben. 2021. Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects. In Journal of medical genetics, 59, 691-696. doi:10.1136/jmedgenet-2021-107775. https://pubmed.ncbi.nlm.nih.gov/34215651/

5. Jat, Kana Ram, Faruq, Mohammed, Jindal, Shishir, Arava, Sudheer K, Kabra, Sushil K. 2024. Genetics of 67 patients of suspected primary ciliary dyskinesia from India. In Clinical genetics, 106, 650-658. doi:10.1111/cge.14590. https://pubmed.ncbi.nlm.nih.gov/39004944/

6. Zlotina, Anna, Barashkova, Svetlana, Zhuk, Sergey, Berleva, Olga, Kostareva, Anna. 2024. Characterization of pathogenic genetic variants in Russian patients with primary ciliary dyskinesia using gene panel sequencing and transcript analysis. In Orphanet journal of rare diseases, 19, 310. doi:10.1186/s13023-024-03318-3. https://pubmed.ncbi.nlm.nih.gov/39180133/

7. Yiallouros, Panayiotis K, Kouis, Panayiotis, Kyriacou, Kyriacos, Loizidou, Maria A, Hadjisavvas, Andreas. 2021. Implementation of multigene panel NGS diagnosis in the national primary ciliary dyskinesia cohort of Cyprus: An island with a high disease prevalence. In Human mutation, 42, e62-e77. doi:10.1002/humu.24196. https://pubmed.ncbi.nlm.nih.gov/33715250/

8. Fassad, Mahmoud R, Shoemark, Amelia, le Borgne, Pierrick, Tassin, Anne-Marie, Mitchison, Hannah M. . C11orf70 Mutations Disrupting the Intraflagellar Transport-Dependent Assembly of Multiple Axonemal Dyneins Cause Primary Ciliary Dyskinesia. In American journal of human genetics, 102, 956-972. doi:10.1016/j.ajhg.2018.03.024. https://pubmed.ncbi.nlm.nih.gov/29727692/

9. Aprea, Isabella, Raidt, Johanna, Höben, Inga Marlena, Kliesch, Sabine, Omran, Heymut. 2021. Defects in the cytoplasmic assembly of axonemal dynein arms cause morphological abnormalities and dysmotility in sperm cells leading to male infertility. In PLoS genetics, 17, e1009306. doi:10.1371/journal.pgen.1009306. https://pubmed.ncbi.nlm.nih.gov/33635866/