{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T19:00:29Z","timestamp":1766516429375,"version":"3.37.3"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006752","name":"Universidade do Porto","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006752","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Assist Reprod Genet"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Propose<\/jats:title>\n                <jats:p>We here present a female case with primary ciliary dyskinesia (PCD) and infertility. In this report, we also present the evaluation of the patient family, including her twin sister, also with PCD and infertility.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Confirmation of the PCD clinical diagnosis was performed through assessment of cilia motility, by high-speed video microscopy (HSVM), axoneme ultrastructure, by transmission electron microscopy (TEM), and genetic characterization, by whole-exome sequence (WES). Gene expression studies used qPCR for mRNA expression and immunofluorescence to determine cell protein localization.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We identified a homozygous nonsense variant in the <jats:italic>DRC1<\/jats:italic> gene (NM 145038.5:c.352C&gt;T (p.Gln118Ter)) in the female patient with PCD and infertility that fit the model of autosomal recessive genetic transmission. This variant eventually results in a dyskinetic ciliary beat with a lower frequency and a partial lack of both dynein arms as revealed by TEM analysis. Moreover, this variant implies a decrease in the expression of <jats:italic>DRC1<\/jats:italic> mRNA and protein. Additionally, expression analysis suggested that <jats:italic>DRC1<\/jats:italic> may interact with other DRC elements.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings suggest that the <jats:italic>DRC1<\/jats:italic> null variant leads to PCD associated with infertility, likely caused by defects in axoneme from Fallopian tube cilia. Overall, our outcomes contribute to a better understanding of the genetic factors involved in the pathophysiology of PCD and infertility, and they highlight the interaction of different genes in the patient phenotype, which should be investigated further because it may explain the high heterogeneity observed in PCD patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10815-023-02755-6","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T06:04:01Z","timestamp":1677650641000},"page":"765-778","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Characterization of a DRC1 null variant associated with primary ciliary dyskinesia and female infertility"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8434-5086","authenticated-orcid":false,"given":"R.","family":"Pereira","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8579-1400","authenticated-orcid":false,"given":"V.","family":"Carvalho","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6985-9580","authenticated-orcid":false,"given":"C.","family":"Dias","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4641-2898","authenticated-orcid":false,"given":"T.","family":"Barbosa","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3924-6385","authenticated-orcid":false,"given":"J.","family":"Oliveira","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9580-6191","authenticated-orcid":false,"given":"\u00c2.","family":"Alves","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8482-5047","authenticated-orcid":false,"given":"E.","family":"Oliveira","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-3822","authenticated-orcid":false,"given":"R.","family":"S\u00e1","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-3290","authenticated-orcid":false,"given":"M.","family":"Sousa","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2023,3,1]]},"reference":[{"issue":"9","key":"2755_CR1","doi-asserted-by":"publisher","first-page":"e911","DOI":"10.1002\/mgg3.911","volume":"7","author":"WB Hannah","year":"2019","unstructured":"Hannah WB, et al. The expanding phenotype of OFD1-related disorders: hemizygous loss-of-function variants in three patients with primary ciliary dyskinesia. Mol Genet Genomic Med. 2019;7(9):e911. https:\/\/doi.org\/10.1002\/mgg3.911.","journal-title":"Mol Genet Genomic Med."},{"issue":"1","key":"2755_CR2","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.ajhg.2016.11.019","volume":"100","author":"T Paff","year":"2017","unstructured":"Paff T, et al. Mutations in PIH1D3 cause X-linked primary ciliary dyskinesia with outer and inner dynein arm defects. Am J Hum Genet. 2017;100(1):160\u20138. https:\/\/doi.org\/10.1016\/j.ajhg.2016.11.019.","journal-title":"Am J Hum Genet."},{"doi-asserted-by":"publisher","unstructured":"Shapiro AJ, et al. Autosomal dominant variants in FOXJ1 causing primary ciliary dyskinesia in two patients with obstructive hydrocephalus. Mol Genet Genomic Med. 2021. https:\/\/doi.org\/10.1002\/mgg3.1726.","key":"2755_CR3","DOI":"10.1002\/mgg3.1726"},{"issue":"5","key":"2755_CR4","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1016\/j.ajhg.2019.09.022","volume":"105","author":"J Wallmeier","year":"2019","unstructured":"Wallmeier J, et al. De novo mutations in FOXJ1 result in a motile ciliopathy with hydrocephalus and randomization of left\/right body asymmetry. Am J Hum Genet. 2019;105(5):1030\u20139. https:\/\/doi.org\/10.1016\/j.ajhg.2019.09.022.","journal-title":"Am J Hum Genet."},{"doi-asserted-by":"publisher","unstructured":"Ardura-Garcia C, et al. Registries and collaborative studies for primary ciliary dyskinesia in Europe. ERJ Open Res. 2020;6(2). https:\/\/doi.org\/10.1183\/23120541.00005-2020.","key":"2755_CR5","DOI":"10.1183\/23120541.00005-2020"},{"issue":"5","key":"2755_CR6","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, et al. The global prevalence and ethnic heterogeneity of primary ciliary dyskinesia gene variants: a genetic database analysis. Lancet Respir Med. 2022;10(5):459\u201368. https:\/\/doi.org\/10.1016\/S2213-2600(21)00453-7.","journal-title":"Lancet Respir Med."},{"doi-asserted-by":"publisher","unstructured":"Pereira R, et al. Clinical and genetic analysis of children with Kartagener syndrome. Cells. 2019;8(8). https:\/\/doi.org\/10.3390\/cells8080900.","key":"2755_CR7","DOI":"10.3390\/cells8080900"},{"issue":"5789","key":"2755_CR8","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1126\/science.1128618","volume":"313","author":"D Nicastro","year":"2006","unstructured":"Nicastro D, et al. The molecular architecture of axonemes revealed by cryoelectron tomography. Science. 2006;313(5789):944\u20138. https:\/\/doi.org\/10.1126\/science.1128618.","journal-title":"Science"},{"issue":"4","key":"2755_CR9","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/j.cell.2019.09.030","volume":"179","author":"M Ma","year":"2019","unstructured":"Ma M, et al. Structure of the decorated ciliary doublet microtubule. Cell. 2019;179(4):909\u2013922.e12. https:\/\/doi.org\/10.1016\/j.cell.2019.09.030.","journal-title":"Cell."},{"key":"2755_CR10","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1083\/jcb.200908067","volume":"187","author":"T Heuser","year":"2009","unstructured":"Heuser T, et al. The dynein regulatory complex is the nexin link and a major regulatory node in cilia and flagella. J Cell Biol. 2009;187:921\u201333. https:\/\/doi.org\/10.1083\/jcb.200908067.","journal-title":"J Cell Biol."},{"issue":"1","key":"2755_CR11","doi-asserted-by":"publisher","first-page":"1601090","DOI":"10.1183\/13993003.01090-2016","volume":"49","author":"JS Lucas","year":"2017","unstructured":"Lucas JS, et al. European Respiratory Society guidelines for the diagnosis of Primary Ciliary Dyskinesia. Eur Respir J. 2017;49(1):1601090. https:\/\/doi.org\/10.1183\/13993003.01090-2016.","journal-title":"Eur Respir J."},{"key":"2755_CR12","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1007\/s10815-019-01509-7","volume":"36","author":"R Pereira","year":"2019","unstructured":"Pereira R, et al. Characterization of CCDC103 expression profiles: further insights in primary ciliary dyskinesia and in human reproduction. J Assist Reprod Genet. 2019;36:1683\u2013700. https:\/\/doi.org\/10.1007\/s10815-019-01509-7.","journal-title":"J Assist Reprod Genet."},{"issue":"5","key":"2755_CR13","doi-asserted-by":"publisher","first-page":"1700314","DOI":"10.1183\/13993003.00314-2017","volume":"50","author":"GJ Vanaken","year":"2017","unstructured":"Vanaken GJ, et al. Infertility in an adult cohort with primary ciliary dyskinesia: phenotype\u2013gene association. Eur Respir J. 2017;50(5):1700314. https:\/\/doi.org\/10.1183\/13993003.00314-2017.","journal-title":"Eur Respir J."},{"doi-asserted-by":"publisher","unstructured":"Aprea I, et al. Motility of efferent duct cilia aids passage of sperm cells through the male reproductive system. Mol Hum Reprod. 2021;27(3). https:\/\/doi.org\/10.1093\/molehr\/gaab009.","key":"2755_CR14","DOI":"10.1093\/molehr\/gaab009"},{"doi-asserted-by":"publisher","unstructured":"Terr\u00e9 B, et al. Defects in efferent duct multiciliogenesis underlie male infertility in GEMC1-, MCIDAS- or CCNO-deficient mice. Development. 2019;146(8). https:\/\/doi.org\/10.1242\/dev.162628.","key":"2755_CR15","DOI":"10.1242\/dev.162628"},{"issue":"12","key":"2755_CR16","doi-asserted-by":"publisher","first-page":"2871","DOI":"10.1093\/humrep\/dev227","volume":"30","author":"J Raidt","year":"2015","unstructured":"Raidt J, et al. Ciliary function and motor protein composition of human fallopian tubes. Hum Reprod. 2015;30(12):2871\u201380. https:\/\/doi.org\/10.1093\/humrep\/dev227.","journal-title":"Hum Reprod."},{"key":"2755_CR17","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/1477-7827-8-48","volume":"8","author":"A Bylander","year":"2010","unstructured":"Bylander A, et al. Rapid effects of progesterone on ciliary beat frequency in the mouse fallopian tube. Reprod Biol Endocrinol. 2010;8:48. https:\/\/doi.org\/10.1186\/1477-7827-8-48.","journal-title":"Reprod Biol Endocrinol."},{"issue":"4","key":"2755_CR18","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1093\/humupd\/dml012","volume":"12","author":"RA Lyons","year":"2006","unstructured":"Lyons RA, Saridogan E, Djahanbakhch O. The reproductive significance of human Fallopian tube cilia. Hum Reprod Update. 2006;12(4):363\u201372. https:\/\/doi.org\/10.1093\/humupd\/dml012.","journal-title":"Hum Reprod Update"},{"issue":"3","key":"2755_CR19","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1080\/01443610802058742","volume":"28","author":"M Blyth","year":"2008","unstructured":"Blyth M, Wellesley D. Ectopic pregnancy in primary ciliary dyskinesia. J Obstet Gynaecol. 2008;28(3):358. https:\/\/doi.org\/10.1080\/01443610802058742.","journal-title":"J Obstet Gynaecol."},{"issue":"5","key":"2755_CR20","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1007\/s00439-020-02143-5","volume":"139","author":"S Maddirevula","year":"2020","unstructured":"Maddirevula S, et al. A genomics approach to females with infertility and recurrent pregnancy loss. Hum Genet. 2020;139(5):605\u201313. https:\/\/doi.org\/10.1007\/s00439-020-02143-5.","journal-title":"Hum Genet."},{"issue":"7","key":"2755_CR21","doi-asserted-by":"publisher","first-page":"e14080","DOI":"10.1111\/and.14080","volume":"53","author":"F Akbarian","year":"2021","unstructured":"Akbarian F, et al. A report of pregnancy following ICSI in one of two sisters with familiar primary ciliary dyskinesia. Andrologia. 2021;53(7):e14080. https:\/\/doi.org\/10.1111\/and.14080.","journal-title":"Andrologia."},{"issue":"1","key":"2755_CR22","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.rbmo.2017.03.019","volume":"35","author":"NPM Kuijsters","year":"2017","unstructured":"Kuijsters NPM, et al. Uterine peristalsis and fertility: current knowledge and future perspectives: a review and meta-analysis. Reprod Biomed Online. 2017;35(1):50\u201371. https:\/\/doi.org\/10.1016\/j.rbmo.2017.03.019.","journal-title":"Reprod Biomed Online."},{"issue":"3","key":"2755_CR23","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/ng.2533","volume":"45","author":"M Wirschell","year":"2013","unstructured":"Wirschell M, et al. The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans. Nat Genet. 2013;45(3):262\u20138. https:\/\/doi.org\/10.1038\/ng.2533.","journal-title":"Nat Genet."},{"key":"2755_CR24","first-page":"298","volume-title":"Ciliary and flagellar motility and the nexin-dynein regulatory complex","author":"ME Porter","year":"2018","unstructured":"Porter ME. In: Dyneins SMK, editor. Ciliary and flagellar motility and the nexin-dynein regulatory complex: Academic Press; 2018. p. 298\u2013335."},{"issue":"46","key":"2755_CR25","doi-asserted-by":"publisher","first-page":"23152","DOI":"10.1073\/pnas.1910960116","volume":"116","author":"L Gui","year":"2019","unstructured":"Gui L, et al. Scaffold subunits support associated subunit assembly in the Chlamydomonas ciliary nexin-dynein regulatory complex. Proc Natl Acad Sci U S A. 2019;116(46):23152\u201362. https:\/\/doi.org\/10.1073\/pnas.1910960116.","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"2","key":"2755_CR26","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1091\/mbc.E17-08-0510","volume":"29","author":"R Bower","year":"2018","unstructured":"Bower R, et al. DRC2\/CCDC65 is a central hub for assembly of the nexin-dynein regulatory complex and other regulators of ciliary and flagellar motility. Mol Biol Cell. 2018;29(2):137\u201353. https:\/\/doi.org\/10.1091\/mbc.E17-08-0510.","journal-title":"Mol Biol Cell."},{"key":"2755_CR27","volume-title":"WHO laboratory manual for the examination and processing of human semen","author":"WHO","year":"2021","unstructured":"WHO. WHO laboratory manual for the examination and processing of human semen. 6th ed. Geneva: WHO; 2021.","edition":"6"},{"issue":"6","key":"2755_CR28","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1093\/humrep\/der037","volume":"26","author":"Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology","year":"2011","unstructured":"Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting\u2020. Hum Reprod. 2011;26(6):1270\u201383. https:\/\/doi.org\/10.1093\/humrep\/der037.","journal-title":"Hum Reprod."},{"issue":"9","key":"2755_CR29","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1093\/humrep\/dex234","volume":"32","author":"F Zegers-Hochschild","year":"2017","unstructured":"Zegers-Hochschild F, et al. The International Glossary on Infertility and Fertility Care, 2017. Hum Reprod. 2017;32(9):1786\u2013801. https:\/\/doi.org\/10.1093\/humrep\/dex234.","journal-title":"Hum Reprod."},{"key":"2755_CR30","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3109\/10409238509086788","volume":"19","author":"BA Afzelius","year":"1985","unstructured":"Afzelius BA, Srurgess JM. The immotile-cilia syndrome: a microtubule-associated defect. Crit Rev Biochem Mol Biol. 1985;19:63\u201387. https:\/\/doi.org\/10.3109\/10409238509086788.","journal-title":"Crit Rev Biochem Mol Biol."},{"issue":"4","key":"2755_CR31","doi-asserted-by":"publisher","first-page":"1900725","DOI":"10.1183\/13993003.00725-2019","volume":"57","author":"A Shoemark","year":"2020","unstructured":"Shoemark A, et al. International consensus guideline for reporting transmission electron microscopy results in the diagnosis of Primary Ciliary Dyskinesia (BEAT PCD TEM Criteria). Eur Respir J. 2020;57(4):1900725. https:\/\/doi.org\/10.1183\/13993003.00725-2019.","journal-title":"Eur Respir J."},{"issue":"6","key":"2755_CR32","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1136\/jcp.42.6.613","volume":"42","author":"R De Iongh","year":"1989","unstructured":"De Iongh R, Rutland J. Orientation of respiratory tract cilia in patients with primary ciliary dyskinesia, bronchiectasis, and in normal subjects. J Clin Pathol. 1989;42(6):613\u20139. https:\/\/doi.org\/10.1136\/jcp.42.6.613.","journal-title":"J Clin Pathol."},{"issue":"4","key":"2755_CR33","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1136\/thorax.55.4.314","volume":"55","author":"MA Chilvers","year":"2000","unstructured":"Chilvers MA, O\u2019Callaghan C. Analysis of ciliary beat pattern and beat frequency using digital high speed imaging: comparison with the photomultiplier and photodiode methods. Thorax. 2000;55(4):314\u20137. https:\/\/doi.org\/10.1136\/thorax.55.4.314.","journal-title":"Thorax."},{"issue":"7","key":"2755_CR34","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671\u20135. https:\/\/doi.org\/10.1038\/nmeth.2089.","journal-title":"Nat Methods."},{"doi-asserted-by":"publisher","unstructured":"Sampaio P, et al. CiliarMove: new software for evaluating ciliary beat frequency helps find novel mutations by a Portuguese multidisciplinary team on primary ciliary dyskinesia. ERJ Open Res. 2021;7(1). https:\/\/doi.org\/10.1183\/23120541.00792-2020.","key":"2755_CR35","DOI":"10.1183\/23120541.00792-2020"},{"issue":"5","key":"2755_CR36","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1016\/j.chest.2016.09.015","volume":"151","author":"C Kempeneers","year":"2017","unstructured":"Kempeneers C, Seaton C, Chilvers MA. Variation of ciliary beat pattern in three different beating planes in healthy subjects. Chest. 2017;151(5):993\u20131001. https:\/\/doi.org\/10.1016\/j.chest.2016.09.015.","journal-title":"Chest."},{"key":"2755_CR37","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/s0091-6749(03)01799-8","volume":"112","author":"MA Chilvers","year":"2003","unstructured":"Chilvers MA, Rutman A, O\u2019Callaghan C. Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia. J Allergy Clin Immunol. 2003;112:518\u201324. https:\/\/doi.org\/10.1016\/s0091-6749(03)01799-8.","journal-title":"J Allergy Clin Immunol"},{"issue":"3","key":"2755_CR38","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","volume":"16","author":"SA Miller","year":"1988","unstructured":"Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215. https:\/\/doi.org\/10.1093\/nar\/16.3.1215.","journal-title":"Nucleic Acids Res."},{"key":"2755_CR39","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s13073-015-0228-1","volume":"7","author":"L Pongor","year":"2015","unstructured":"Pongor L, et al. A genome-wide approach to link genotype to clinical outcome by utilizing next generation sequencing and gene chip data of 6,697 breast cancer patients. Genome Med. 2015;7:104. https:\/\/doi.org\/10.1186\/s13073-015-0228-1.","journal-title":"Genome Med."},{"issue":"9","key":"2755_CR40","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","volume":"29","author":"M Pfaffl","year":"2001","unstructured":"Pfaffl M. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29(9):e45. https:\/\/doi.org\/10.1093\/nar\/29.9.e45.","journal-title":"Nucleic Acids Res."},{"issue":"2","key":"2755_CR41","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s00431-012-1785-6","volume":"172","author":"M Boon","year":"2013","unstructured":"Boon M, et al. Primary ciliary dyskinesia, an orphan disease. Eur J Pediatr. 2013;172(2):151\u201362. https:\/\/doi.org\/10.1007\/s00431-012-1785-6.","journal-title":"Eur J Pediatr"},{"issue":"5","key":"2755_CR42","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201324. https:\/\/doi.org\/10.1038\/gim.2015.30.","journal-title":"Genet Med."},{"issue":"2","key":"2755_CR43","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/ng817","volume":"30","author":"H Olbrich","year":"2002","unstructured":"Olbrich H, et al. Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. Nat Genet. 2002;30(2):143\u20134. https:\/\/doi.org\/10.1038\/ng817.","journal-title":"Nat Genet."},{"issue":"5","key":"2755_CR44","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1016\/j.ajhg.2012.10.003","volume":"91","author":"E Kott","year":"2012","unstructured":"Kott E, et al. Loss-of-function mutations in LRRC6, a gene essential for proper axonemal assembly of inner and outer dynein arms, cause primary ciliary dyskinesia. Am J Hum Genet. 2012;91(5):958\u201364. https:\/\/doi.org\/10.1016\/j.ajhg.2012.10.003.","journal-title":"Am J Hum Genet."},{"issue":"2","key":"2755_CR45","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.ajhg.2009.01.011","volume":"84","author":"VH Castleman","year":"2009","unstructured":"Castleman VH, et al. Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities. Am J Hum Genet. 2009;84(2):197\u2013209. https:\/\/doi.org\/10.1016\/j.ajhg.2009.01.011.","journal-title":"Am J Hum Genet."},{"issue":"4","key":"2755_CR46","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/s10038-021-00985-z","volume":"67","author":"C Lei","year":"2022","unstructured":"Lei C, et al. DRC1 deficiency caused primary ciliary dyskinesia and MMAF in a Chinese patient. J Hum Genet. 2022;67(4):197\u2013201. https:\/\/doi.org\/10.1038\/s10038-021-00985-z.","journal-title":"J Hum Genet."},{"doi-asserted-by":"publisher","unstructured":"Liu Y, et al. Case report: whole-exome sequencing-based copy number variation analysis identified a novel DRC1 homozygous exon deletion in a patient with primary ciliary dyskinesia. Front Genet. 2022;13. https:\/\/doi.org\/10.3389\/fgene.2022.940292.","key":"2755_CR47","DOI":"10.3389\/fgene.2022.940292"},{"doi-asserted-by":"publisher","unstructured":"Jiang G, et al. Homozygous mutation in DNAAF4 causes primary ciliary dyskinesia in a Chinese family. Front Genet. 2022;13. https:\/\/doi.org\/10.3389\/fgene.2022.1087818.","key":"2755_CR48","DOI":"10.3389\/fgene.2022.1087818"},{"key":"2755_CR49","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.2147\/pgpm.S338981","volume":"14","author":"C Lu","year":"2021","unstructured":"Lu C, et al. Identification of two novel DNAAF2 variants in two consanguineous families with primary ciliary dyskinesia. Pharmgenomics Pers Med. 2021;14:1415\u201323. https:\/\/doi.org\/10.2147\/pgpm.S338981.","journal-title":"Pharmgenomics Pers Med."},{"doi-asserted-by":"publisher","unstructured":"Wang R, et al. Case report: identification of a novel ODAD3 variant in a patient with primary ciliary dyskinesia. Front Genet. 2021;12. https:\/\/doi.org\/10.3389\/fgene.2021.652381.","key":"2755_CR50","DOI":"10.3389\/fgene.2021.652381"},{"key":"2755_CR51","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/ng.727","volume":"43","author":"A Becker-Heck","year":"2011","unstructured":"Becker-Heck A, et al. The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation. Nat Genet. 2011;43:79\u201384. https:\/\/doi.org\/10.1038\/ng.727.","journal-title":"Nat Genet."},{"key":"2755_CR52","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/ng.726","volume":"43","author":"A-C Merveille","year":"2011","unstructured":"Merveille A-C, et al. CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs. Nat Genet. 2011;43:72\u20138. https:\/\/doi.org\/10.1038\/ng.726.","journal-title":"Nat Genet."},{"issue":"8","key":"2755_CR53","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1002\/humu.24221","volume":"42","author":"M Lopes-Marques","year":"2021","unstructured":"Lopes-Marques M, et al. Common polymorphic OTC variants can act as genetic modifiers of enzymatic activity. Hum Mutat. 2021;42(8):978\u201389. https:\/\/doi.org\/10.1002\/humu.24221.","journal-title":"Hum Mutat."},{"issue":"7751","key":"2755_CR54","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41586-019-1064-z","volume":"568","author":"MA El-Brolosy","year":"2019","unstructured":"El-Brolosy MA, et al. Genetic compensation triggered by mutant mRNA degradation. Nature. 2019;568(7751):193\u20137. https:\/\/doi.org\/10.1038\/s41586-019-1064-z.","journal-title":"Nature."},{"key":"2755_CR55","volume-title":"Primary ciliary dyskinesia","author":"M Zariwala","year":"2013","unstructured":"Zariwala M, Knowles M, Leigh M. Primary ciliary dyskinesia: GeneReviews\u2122; 2013. Updated 2019 Dec 5 [cited 2021 30\/6\/2021]; Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1122\/#"},{"doi-asserted-by":"publisher","unstructured":"Morimoto K, et al. Recurring large deletion in DRC1 (CCDC164) identified as causing primary ciliary dyskinesia in two Asian patients. Mol Genet Genomic Med. 2019;7(8). https:\/\/doi.org\/10.1002\/mgg3.838.","key":"2755_CR56","DOI":"10.1002\/mgg3.838"},{"issue":"1","key":"2755_CR57","doi-asserted-by":"publisher","first-page":"e1033","DOI":"10.1002\/mgg3.1033","volume":"8","author":"N Keicho","year":"2020","unstructured":"Keicho N, et al. Primary ciliary dyskinesia caused by a large homozygous deletion including exons 1-4 of DRC1 in Japanese patients with recurrent sinopulmonary infection. Mol Genet Genomic Med. 2020;8(1):e1033. https:\/\/doi.org\/10.1002\/mgg3.1033.","journal-title":"Mol Genet Genomic Med."},{"doi-asserted-by":"publisher","unstructured":"Takeuchi K, et al. Copy number variation in DRC1 is the major cause of primary ciliary dyskinesia in the Japanese population. Mol Genet Genomic Med. 2020;8(3). https:\/\/doi.org\/10.1002\/mgg3.1137.","key":"2755_CR58","DOI":"10.1002\/mgg3.1137"},{"issue":"2","key":"2755_CR59","doi-asserted-by":"publisher","first-page":"179","DOI":"10.4103\/lungindia.lungindia_361_19","volume":"37","author":"A Benjamin","year":"2020","unstructured":"Benjamin A, et al. Primary ciliary dyskinesia due to DRC1\/CCDC164 gene mutation. Lung India. 2020;37(2):179\u201380. https:\/\/doi.org\/10.4103\/lungindia.lungindia_361_19.","journal-title":"Lung India."},{"issue":"1","key":"2755_CR60","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/humu.23905","volume":"41","author":"R Mani","year":"2020","unstructured":"Mani R, et al. Primary ciliary dyskinesia gene contribution in Tunisia: Identification of a major Mediterranean allele. Hum Mutat. 2020;41(1):115\u201321. https:\/\/doi.org\/10.1002\/humu.23905.","journal-title":"Hum Mutat."},{"issue":"suppl 61","key":"2755_CR61","doi-asserted-by":"publisher","first-page":"PA1851","DOI":"10.1183\/1393003.congress-2017.PA1851","volume":"50","author":"A Shoemark","year":"2017","unstructured":"Shoemark A, et al. A high prevalence CCDC103 p.His154Pro mutation causing primary ciliary dyskinesia is associated with normal diagnostic investigations. Eur Respir J. 2017;50(suppl 61):PA1851. https:\/\/doi.org\/10.1183\/1393003.congress-2017.PA1851.","journal-title":"Eur Respir J."},{"doi-asserted-by":"publisher","unstructured":"Long H, Huang K. Transport of ciliary membrane proteins. Front Cell Dev Biol. 2020;7(381). https:\/\/doi.org\/10.3389\/fcell.2019.00381.","key":"2755_CR62","DOI":"10.3389\/fcell.2019.00381"},{"issue":"7","key":"2755_CR63","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.tig.2020.11.002","volume":"37","author":"F Supek","year":"2021","unstructured":"Supek F, Lehner B, Lindeboom RGH. To NMD or not to NMD: nonsense-mediated mRNA decay in cancer and other genetic diseases. Trends Genet. 2021;37(7):657\u201368. https:\/\/doi.org\/10.1016\/j.tig.2020.11.002.","journal-title":"Trends Genet."}],"container-title":["Journal of Assisted Reproduction and Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10815-023-02755-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10815-023-02755-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10815-023-02755-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T06:05:28Z","timestamp":1685167528000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10815-023-02755-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,1]]},"references-count":63,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["2755"],"URL":"https:\/\/doi.org\/10.1007\/s10815-023-02755-6","relation":{},"ISSN":["1058-0468","1573-7330"],"issn-type":[{"type":"print","value":"1058-0468"},{"type":"electronic","value":"1573-7330"}],"subject":[],"published":{"date-parts":[[2023,3,1]]},"assertion":[{"value":"5 December 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have followed all the rules of ethical conduct regarding originality, data processing and analysis, duplicate publication, and biological material. Biological material from the patient, family members, and controls was obtained after written informed consent and used in experiments according to the Joint Ethics Committee of the Hospital and University, CHUP\/ICBAS approval number 2020-094 (077-DEFI-078-CE).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable. This manuscript does not contain any individual person\u2019s data, only clinical data entirely unidentifiable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}