{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DNAH14 encodes a dynein axonemal heavy chain protein that plays an important role in the structure and function of motile cilia. Its involvement in ciliary motility has been highlighted by the identification of rare mutations in patients with primary ciliary dyskinesia, suggesting that disruption of DNAH14 may contribute to impaired ciliary beating and related respiratory dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In cystic fibrosis, genetic variants in DNAH14 have been associated with both poor and preserved lung function, implying a modulatory role in airway clearance via ciliary activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its contribution to ciliary motion, compound heterozygous variants in DNAH14 have been linked to neurodevelopmental disorders characterized by seizures, global developmental delay, microcephaly, and hypotonia, underscoring its importance in normal brain development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the field of oncology, specific single nucleotide variants in DNAH14 (e.g., rs3105571) have been associated with an improved pathological complete response in locally advanced rectal cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "and with better survival in ovarian cancer patients"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", indicating its potential utility as a biomarker."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, structural aberrations in DNAH14 have been observed in other developmental contexts. A deletion in DNAH14 was found to co-segregate with a familial form of panventriculomegaly and features of congenital hydrocephalus, suggesting that disruptions in ciliary-driven cerebrospinal fluid flow contribute to neurological pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, identification of DNAH14 among novel candidate genes in consanguineous families exhibiting embryonic lethality further supports its key role in early human development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, while variants in DNAH14 have been observed in other cancers such as melanoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and as part of the broader mutational profile of the DNAH gene family in gastric adenocarcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", further studies are needed to clarify its oncogenic or tumor suppressive roles. Collectively, these studies reveal that DNAH14 is a multifaceted gene whose normal function in ciliary motility has far‐reaching implications in respiratory, neurological, developmental, and oncological processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yuhong Guan, Haiming Yang, Xingfeng Yao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical and Genetic Spectrum of Children With Primary Ciliary Dyskinesia in China."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chest (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.chest.2021.02.006"}], "href": "https://doi.org/10.1016/j.chest.2021.02.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33577779"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33577779"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Elizabeth Blue, Tin L Louie, Jessica X Chong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variation in Cilia Protein Genes and Progression of Lung Disease in Cystic Fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Am Thorac Soc (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1513/AnnalsATS.201706-451OC"}], "href": "https://doi.org/10.1513/AnnalsATS.201706-451OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29323929"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29323929"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Juan Li, Yu Yuan, Chaorong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNAH14 variants are associated with neurodevelopmental disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.24386"}], "href": "https://doi.org/10.1002/humu.24386"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35438214"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35438214"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "In Hee Lee, Keunsoo Kang, Byung Woog Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variations using whole-exome sequencing might predict response for neoadjuvant chemoradiotherapy in locally advanced rectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Oncol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12032-018-1202-8"}], "href": "https://doi.org/10.1007/s12032-018-1202-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30206710"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30206710"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rosemary Braun, Richard Finney, Chunhua Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Discovery analysis of TCGA data reveals association between germline genotype and survival in ovarian cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0055037"}], "href": "https://doi.org/10.1371/journal.pone.0055037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23555554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23555554"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shigeki Yamada, Masatsune Ishikawa, Kazuo Yamamoto "}, {"type": "b", "children": [{"type": "t", "text": "Fluid Distribution Pattern in Adult-Onset Congenital, Idiopathic, and Secondary Normal-Pressure Hydrocephalus: Implications for Clinical Care."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Neurol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fneur.2017.00583"}], "href": "https://doi.org/10.3389/fneur.2017.00583"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29163345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29163345"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hanan E Shamseldin, Maha Tulbah, Wesam Kurdi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of embryonic lethal genes in humans by autozygosity mapping and exome sequencing in consanguineous families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genome Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13059-015-0681-6"}], "href": "https://doi.org/10.1186/s13059-015-0681-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26036949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26036949"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Tadeusz Dębniak, Rodney J Scott, Rodney A Lea, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Founder Mutations for Early Onset Melanoma as Revealed by Whole Exome Sequencing Suggests That This is Not Associated with the Increasing Incidence of Melanoma in Poland."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res Treat (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4143/crt.2018.157"}], "href": "https://doi.org/10.4143/crt.2018.157"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29764119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29764119"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Chunchao Zhu, Qin Yang, Jia Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Somatic mutation of DNAH genes implicated higher chemotherapy response rate in gastric adenocarcinoma patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-019-1867-6"}], "href": "https://doi.org/10.1186/s12967-019-1867-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30944005"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30944005"}]}]}]}