Clinical and Genetic Analysis of Children with Kartagener Syndrome
Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterized by dysfunction of motile cilia causing ineffective mucus clearance and organ laterality defects. In this study, two unrelated Portuguese children with strong PCD suspicion underwent extensive clinical and genetic a...
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MDPI AG
2019-08-01
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| Online Access: | https://www.mdpi.com/2073-4409/8/8/900 |
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| author | Rute Pereira Telma Barbosa Luís Gales Elsa Oliveira Rosário Santos Jorge Oliveira Mário Sousa |
| author_facet | Rute Pereira Telma Barbosa Luís Gales Elsa Oliveira Rosário Santos Jorge Oliveira Mário Sousa |
| author_sort | Rute Pereira |
| collection | DOAJ |
| description | Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterized by dysfunction of motile cilia causing ineffective mucus clearance and organ laterality defects. In this study, two unrelated Portuguese children with strong PCD suspicion underwent extensive clinical and genetic assessments by whole-exome sequencing (WES), as well as ultrastructural analysis of cilia by transmission electron microscopy (TEM) to identify their genetic etiology. These analyses confirmed the diagnostic of Kartagener syndrome (KS) (PCD with <i>situs inversus</i>). Patient-1 showed a predominance of the absence of the inner dynein arms with two disease-causing variants in the <i>CCDC40</i> gene. Patient-2 showed the absence of both dynein arms and WES disclosed two novel high impact variants in the <i>DNAH5</i> gene and two missense variants in the <i>DNAH7</i> gene, all possibly deleterious. Moreover, in Patient-2, functional data revealed a reduction of gene expression and protein mislocalization in both genes’ products. Our work calls the researcher’s attention to the complexity of the PCD and to the possibility of gene interactions modelling the PCD phenotype. Further, it is demonstrated that even for well-known PCD genes, novel pathogenic variants could have importance for a PCD/KS diagnosis, reinforcing the difficulty of providing genetic counselling and prenatal diagnosis to families. |
| first_indexed | 2024-03-12T06:15:17Z |
| format | Article |
| id | doaj.art-04be531c976740afabe5fe71e66e214c |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T06:15:17Z |
| publishDate | 2019-08-01 |
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| spelling | doaj.art-04be531c976740afabe5fe71e66e214c2023-09-03T02:37:01ZengMDPI AGCells2073-44092019-08-018890010.3390/cells8080900cells8080900Clinical and Genetic Analysis of Children with Kartagener SyndromeRute Pereira0Telma Barbosa1Luís Gales2Elsa Oliveira3Rosário Santos4Jorge Oliveira5Mário Sousa6Laboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto (UP), Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, PortugalDepartment of Pediatrics, Maternal Child Center of the North (CMIN), University Hospital Center of Porto (CHUP), Largo da Maternidade de Júlio Dinis, 4050-651 Porto, PortugalDepartment of Molecular Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto (UP), Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, PortugalLaboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto (UP), Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, PortugalMultidisciplinary Unit for Biomedical Research (UMIB), ICBAS-UP, 4050-313 Porto, PortugalMultidisciplinary Unit for Biomedical Research (UMIB), ICBAS-UP, 4050-313 Porto, PortugalLaboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto (UP), Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, PortugalPrimary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterized by dysfunction of motile cilia causing ineffective mucus clearance and organ laterality defects. In this study, two unrelated Portuguese children with strong PCD suspicion underwent extensive clinical and genetic assessments by whole-exome sequencing (WES), as well as ultrastructural analysis of cilia by transmission electron microscopy (TEM) to identify their genetic etiology. These analyses confirmed the diagnostic of Kartagener syndrome (KS) (PCD with <i>situs inversus</i>). Patient-1 showed a predominance of the absence of the inner dynein arms with two disease-causing variants in the <i>CCDC40</i> gene. Patient-2 showed the absence of both dynein arms and WES disclosed two novel high impact variants in the <i>DNAH5</i> gene and two missense variants in the <i>DNAH7</i> gene, all possibly deleterious. Moreover, in Patient-2, functional data revealed a reduction of gene expression and protein mislocalization in both genes’ products. Our work calls the researcher’s attention to the complexity of the PCD and to the possibility of gene interactions modelling the PCD phenotype. Further, it is demonstrated that even for well-known PCD genes, novel pathogenic variants could have importance for a PCD/KS diagnosis, reinforcing the difficulty of providing genetic counselling and prenatal diagnosis to families.https://www.mdpi.com/2073-4409/8/8/900primary ciliary dyskinesia<i>situs inversus</i>whole-exome sequencing<i>CCDC40</i><i>DNAH5</i><i>DNAH7</i> |
| spellingShingle | Rute Pereira Telma Barbosa Luís Gales Elsa Oliveira Rosário Santos Jorge Oliveira Mário Sousa Clinical and Genetic Analysis of Children with Kartagener Syndrome Cells primary ciliary dyskinesia <i>situs inversus</i> whole-exome sequencing <i>CCDC40</i> <i>DNAH5</i> <i>DNAH7</i> |
| title | Clinical and Genetic Analysis of Children with Kartagener Syndrome |
| title_full | Clinical and Genetic Analysis of Children with Kartagener Syndrome |
| title_fullStr | Clinical and Genetic Analysis of Children with Kartagener Syndrome |
| title_full_unstemmed | Clinical and Genetic Analysis of Children with Kartagener Syndrome |
| title_short | Clinical and Genetic Analysis of Children with Kartagener Syndrome |
| title_sort | clinical and genetic analysis of children with kartagener syndrome |
| topic | primary ciliary dyskinesia <i>situs inversus</i> whole-exome sequencing <i>CCDC40</i> <i>DNAH5</i> <i>DNAH7</i> |
| url | https://www.mdpi.com/2073-4409/8/8/900 |
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