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However, the precise relationship between variant type or location in the <jats:italic>DNAH5<\/jats:italic> gene and the clinical heterogeneity remains elusive. The present systematic review aims to provide critical insights into the impact of the molecular nature of <jats:italic>DNAH5<\/jats:italic> variants on PCD phenotypes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We enrolled all reported cases of PCD with biallelic pathogenic variants in the <jats:italic>DNAH5<\/jats:italic> gene to date, and evaluated genotype\u2013phenotype correlations in these patients, employing truncating (TV) and missense (MV) variant-carrying as grouping criteria.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>A total of 323 PCD patients with the <jats:italic>DNAH5<\/jats:italic> variants were included, with 14.55% of these patients were diagnosed as Kartagener syndrome. Pediatric and adult patients exhibited distinct clinical features, including varying incidences of bronchiectasis, infertility, neonatal respiratory distress (NRD), ciliary ultrastructural defects distributions, and lung function (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). With regard to mutational patterns, truncating variants in <jats:italic>DNAH5<\/jats:italic> were clustered in the 1200\u20133200 amino acid region, and were more prevalent in children compared to adult (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Most missense variants are clustering in the linker, AAA\u2009+\u2009ATPase and AAA-lid domains. The most frequently observed mutation, c.10815delT, was prevalent in Europe and America, whereas c.8030G\u2009&gt;\u2009A was more common in China and Asia. In terms of genotype\u2013phenotype correlations, individuals with the TV\/TV genotype exhibited a higher proportion of NRD and earlier onset compared to those with MV-carrying genotypes, both in overall population and in pediatric patients (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Patients with the TV\/TV genotype exhibited worse lung function compared to those with MV-carrying genotypes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The study underscores the broad mutational spectrum and high phenotypic heterogenicity in <jats:italic>DNAH5<\/jats:italic>-related PCD patients. The presence of biallelic truncating variants may predispose patients to earlier disease onset and poorer lung function.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13023-025-03596-5","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T11:21:06Z","timestamp":1741000866000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Genetic spectrum and genotype\u2013phenotype correlations in DNAH5-mutated primary ciliary dyskinesia: a systematic review"],"prefix":"10.1186","volume":"20","author":[{"given":"Meihua","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jielin","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7164-6947","authenticated-orcid":false,"given":"Nan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"issue":"5","key":"3596_CR1","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/S2213-2600(21)00453-7","volume":"10","author":"WB Hannah","year":"2022","unstructured":"Hannah WB, Seifert BA, Truty R, et al. 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