Dnah14-KO Mouse

DNAH14, whose functions are still being actively investigated, may be involved in cilia-related functions given its association with primary ciliary dyskinesia (PCD) [2,3]. Cilia are important cellular structures involved in processes such as mucociliary clearance. In addition, it may play a role in neurodevelopment as its variants have been linked to neurodevelopmental disorders (NDD) [1].

Compound heterozygous DNAH14 variants were identified in three unrelated patients with NDD. These variants included nonsense, frameshift, and missense mutations, some located in the AAA+ ATPase domain and others in the C-terminal domain. The affected amino acids were highly conserved across species, and patients presented with phenotypes like seizures, global developmental delay, microcephaly, and hypotonia [1]. An association between DNAH14 and PCD was observed in Chinese and Indian patients, expanding the PCD genotypic spectrum [2,3]. Also, variants in DNAH14 were associated with both poor and preserved lung function in cystic fibrosis [4].

In conclusion, DNAH14 appears to be crucial in neurodevelopment and cilia-related functions. Its variants are associated with NDD and PCD, as well as with variation in lung function in cystic fibrosis patients. Studies on DNAH14 contribute to understanding the genetic basis of these diseases, potentially paving the way for more targeted diagnostic and treatment strategies.

References:

1. Li, Juan, Yuan, Yu, Liu, Chaorong, Mao, Xiao, Long, Lili. 2022. DNAH14 variants are associated with neurodevelopmental disorders. In Human mutation, 43, 940-949. doi:10.1002/humu.24386. https://pubmed.ncbi.nlm.nih.gov/35438214/

2. Guan, Yuhong, Yang, Haiming, Yao, Xingfeng, Ge, Wentong, Ni, Xin. 2021. Clinical and Genetic Spectrum of Children With Primary Ciliary Dyskinesia in China. In Chest, 159, 1768-1781. doi:10.1016/j.chest.2021.02.006. https://pubmed.ncbi.nlm.nih.gov/33577779/

3. 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/

4. Blue, Elizabeth, Louie, Tin L, Chong, Jessica X, Bamshad, Michael J, Emond, Mary J. . Variation in Cilia Protein Genes and Progression of Lung Disease in Cystic Fibrosis. In Annals of the American Thoracic Society, 15, 440-448. doi:10.1513/AnnalsATS.201706-451OC. https://pubmed.ncbi.nlm.nih.gov/29323929/