Publicação
Primary ciliary dyskinesia due to CCNO mutations : a genotype‐phenotype correlation contribution
| Resumo: | Primary ciliary dyskinesia (PCD) is genetically and clinically heterogeneous. CCNO mutations are associated with chronic destructive lung disease and were first described in 2014. Early reports suggest that CCNO is mutated more frequently than expected, however, these are considered rare. We report on three eleven-year-old children with PCD due to CCNO mutations. All children presented early-onset respiratory symptoms, no cardiac or situs anomalies and moderate to severe clinical courses. Patients 1 and 3 were admitted to a neonatal intensive care unit due to respiratory distress. Patients 1 and 2 had atelectasis and lobar collapse, for which lobectomy was performed for patient 1. Patient 3 also presented otitis media with effusion with conductive hearing loss, requiring tympanostomy tube insertion twice. Diagnosis of PCD for all three required repeated nasal brushings, delaying diagnostic confirmation. Microscopy analysis revealed severely decreased numbers of cilia, but normal ultrastructure and uncoordinated beat pattern in the residual cilia. Surprisingly, the prevalence of pathogenic CCNO variants in our centre is higher than expected (three out of sixteen patients). Pathogenic variants in PCD-causing genes lead to specific ultrastructural defects, and there is a suggestion for genotype-phenotype association. However, there are little longitudinal data evaluating the impact of specific defects on disease progression, but a recent study showed a worse lung disease and poorer nutritional status. Concluding, this report underlies the importance of patient-oriented diagnosis and management in highly experienced PCD centres. |
|---|---|
| Autores principais: | Henriques, Ana Raquel |
| Outros Autores: | Constant, Carolina; Descalço, Andreia; Pinto, Andreia; Moura Nunes, J.; Sampaio, Pedro; Lopes, Susana S.; Pereira, Luísa; Bandeira, Teresa |
| Assunto: | CCNO mutations Child Chronic diseases Ciliary motility disorders |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| _version_ | 1866809840208183296 |
|---|---|
| author | Henriques, Ana Raquel |
| author2 | Constant, Carolina Descalço, Andreia Pinto, Andreia Moura Nunes, J. Sampaio, Pedro Lopes, Susana S. Pereira, Luísa Bandeira, Teresa |
| author2_role | author author author author author author author author |
| author_facet | Henriques, Ana Raquel Constant, Carolina Descalço, Andreia Pinto, Andreia Moura Nunes, J. Sampaio, Pedro Lopes, Susana S. Pereira, Luísa Bandeira, Teresa |
| author_role | author |
| contributor_name_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Henriques, Ana Raquel\"},{\"Person.name\":\"Constant, Carolina\",\"Person.identifier.orcid\":\"0000-0002-6596-1596\"},{\"Person.name\":\"Descalço, Andreia\"},{\"Person.name\":\"Pinto, Andreia\",\"Person.identifier.orcid\":\"0000-0002-0840-6844\"},{\"Person.name\":\"Moura Nunes, J.\"},{\"Person.name\":\"Sampaio, Pedro\"},{\"Person.name\":\"Lopes, Susana S.\"},{\"Person.name\":\"Pereira, Luísa\"},{\"Person.name\":\"Bandeira, Teresa\",\"Person.identifier.orcid\":\"0000-0002-6214-3117\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Henriques, Ana Raquel Constant, Carolina Descalço, Andreia Pinto, Andreia Moura Nunes, J. Sampaio, Pedro Lopes, Susana S. Pereira, Luísa Bandeira, Teresa |
| datacite.date.Accepted.fl_str_mv | 2021-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2021-06-21T16:47:12Z |
| datacite.date.embargoed.fl_str_mv | 2021-06-21T16:47:12Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| datacite.subjects.subject.fl_str_mv | CCNO mutations Child Chronic diseases Ciliary motility disorders |
| datacite.titles.title.fl_str_mv | Primary ciliary dyskinesia due to CCNO mutations : a genotype‐phenotype correlation contribution |
| dc.contributor.none.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Henriques, Ana Raquel Constant, Carolina Descalço, Andreia Pinto, Andreia Moura Nunes, J. Sampaio, Pedro Lopes, Susana S. Pereira, Luísa Bandeira, Teresa |
| dc.date.Accepted.fl_str_mv | 2021-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2021-06-21T16:47:12Z |
| dc.date.embargoed.fl_str_mv | 2021-06-21T16:47:12Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/48683 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | John Wiley & Sons, Inc. |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| dc.subject.none.fl_str_mv | CCNO mutations Child Chronic diseases Ciliary motility disorders |
| dc.title.fl_str_mv | Primary ciliary dyskinesia due to CCNO mutations : a genotype‐phenotype correlation contribution |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Primary ciliary dyskinesia (PCD) is genetically and clinically heterogeneous. CCNO mutations are associated with chronic destructive lung disease and were first described in 2014. Early reports suggest that CCNO is mutated more frequently than expected, however, these are considered rare. We report on three eleven-year-old children with PCD due to CCNO mutations. All children presented early-onset respiratory symptoms, no cardiac or situs anomalies and moderate to severe clinical courses. Patients 1 and 3 were admitted to a neonatal intensive care unit due to respiratory distress. Patients 1 and 2 had atelectasis and lobar collapse, for which lobectomy was performed for patient 1. Patient 3 also presented otitis media with effusion with conductive hearing loss, requiring tympanostomy tube insertion twice. Diagnosis of PCD for all three required repeated nasal brushings, delaying diagnostic confirmation. Microscopy analysis revealed severely decreased numbers of cilia, but normal ultrastructure and uncoordinated beat pattern in the residual cilia. Surprisingly, the prevalence of pathogenic CCNO variants in our centre is higher than expected (three out of sixteen patients). Pathogenic variants in PCD-causing genes lead to specific ultrastructural defects, and there is a suggestion for genotype-phenotype association. However, there are little longitudinal data evaluating the impact of specific defects on disease progression, but a recent study showed a worse lung disease and poorer nutritional status. Concluding, this report underlies the importance of patient-oriented diagnosis and management in highly experienced PCD centres. |
| dirty | 0 |
| eu_rights_str_mv | restrictedAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ulisboa.pt/bitstreams/4b5c0993-b2d8-4e8f-aa4b-2ccb2131c09c/download |
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| identifier.url.fl_str_mv | http://hdl.handle.net/10451/48683 |
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| institution | Universidade de Lisboa |
| instname_str | Universidade de Lisboa |
| language | eng |
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| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/48683 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Henriques, Ana Raquel Constant, Carolina Constant, Carolina http://orcid.org/0000-0002-6596-1596 0000-0002-6596-1596 Descalço, Andreia Pinto, Andreia Pinto, Andreia http://orcid.org/0000-0002-0840-6844 0000-0002-0840-6844 Moura Nunes, J. Sampaio, Pedro Lopes, Susana S. Pereira, Luísa Bandeira, Teresa Bandeira, Teresa https://www.ciencia-id.pt/7B19-E545-226D 7B19-E545-226D http://orcid.org/0000-0002-6214-3117 0000-0002-6214-3117 |
| publishDate | 2021 |
| publisher.none.fl_str_mv | John Wiley & Sons, Inc. |
| reponame_str | Repositório da Universidade de Lisboa |
| repository_id_str | urn:repositoryAcronym:ul |
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| spelling | engJohn Wiley & Sons, Inc.pt_PTPrimary ciliary dyskinesia (PCD) is genetically and clinically heterogeneous. CCNO mutations are associated with chronic destructive lung disease and were first described in 2014. Early reports suggest that CCNO is mutated more frequently than expected, however, these are considered rare. We report on three eleven-year-old children with PCD due to CCNO mutations. All children presented early-onset respiratory symptoms, no cardiac or situs anomalies and moderate to severe clinical courses. Patients 1 and 3 were admitted to a neonatal intensive care unit due to respiratory distress. Patients 1 and 2 had atelectasis and lobar collapse, for which lobectomy was performed for patient 1. Patient 3 also presented otitis media with effusion with conductive hearing loss, requiring tympanostomy tube insertion twice. Diagnosis of PCD for all three required repeated nasal brushings, delaying diagnostic confirmation. Microscopy analysis revealed severely decreased numbers of cilia, but normal ultrastructure and uncoordinated beat pattern in the residual cilia. Surprisingly, the prevalence of pathogenic CCNO variants in our centre is higher than expected (three out of sixteen patients). Pathogenic variants in PCD-causing genes lead to specific ultrastructural defects, and there is a suggestion for genotype-phenotype association. However, there are little longitudinal data evaluating the impact of specific defects on disease progression, but a recent study showed a worse lung disease and poorer nutritional status. Concluding, this report underlies the importance of patient-oriented diagnosis and management in highly experienced PCD centres.application/pdfpt_PTPrimary ciliary dyskinesia due to CCNO mutations : a genotype‐phenotype correlation contributionHenriques, Ana RaquelPersonalConstant, CarolinaDSpacehttp://dspace.org/items/adcb84cf-9b1d-43ab-ab73-4d1be5881191DSpacehttp://dspace.org/items/adcb84cf-9b1d-43ab-ab73-4d1be5881191ConstantCarolinaORCIDhttp://orcid.org0000-0002-6596-1596Descalço, AndreiaPersonalPinto, AndreiaDSpacehttp://dspace.org/items/eae0f147-b206-4c61-9860-ff60215b9168DSpacehttp://dspace.org/items/eae0f147-b206-4c61-9860-ff60215b9168PintoAndreiaORCIDhttp://orcid.org0000-0002-0840-6844Moura Nunes, J.Sampaio, PedroLopes, Susana S.Pereira, LuísaPersonalBandeira, TeresaDSpacehttp://dspace.org/items/38518bb2-ba58-4ab9-8bab-c4f342f51123DSpacehttp://dspace.org/items/38518bb2-ba58-4ab9-8bab-c4f342f51123BandeiraTeresaCiência IDhttps://www.ciencia-id.pt7B19-E545-226DORCIDhttp://orcid.org0000-0002-6214-3117Researcher IDhttps://www.researcherid.comC-4397-2016Scopus Author IDhttps://www.scopus.com6507931000HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptISSNIsPartOf8755-6863DOIIsPartOf10.1002/ppul.254402021-06-21T16:47:12Z20212021-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/48683http://purl.org/coar/access_right/c_16ecrestricted accessCCNO mutationsChildChronic diseasesCiliary motility disorders295414 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/4b5c0993-b2d8-4e8f-aa4b-2ccb2131c09c/downloadPediatric Pulmonology |
| spellingShingle | Primary ciliary dyskinesia due to CCNO mutations : a genotype‐phenotype correlation contribution Henriques, Ana Raquel CCNO mutations Child Chronic diseases Ciliary motility disorders |
| status | SINGLETON |
| subject.fl_str_mv | CCNO mutations Child Chronic diseases Ciliary motility disorders |
| title | Primary ciliary dyskinesia due to CCNO mutations : a genotype‐phenotype correlation contribution |
| title_full | Primary ciliary dyskinesia due to CCNO mutations : a genotype‐phenotype correlation contribution |
| title_fullStr | Primary ciliary dyskinesia due to CCNO mutations : a genotype‐phenotype correlation contribution |
| title_full_unstemmed | Primary ciliary dyskinesia due to CCNO mutations : a genotype‐phenotype correlation contribution |
| title_short | Primary ciliary dyskinesia due to CCNO mutations : a genotype‐phenotype correlation contribution |
| title_sort | Primary ciliary dyskinesia due to CCNO mutations : a genotype‐phenotype correlation contribution |
| topic | CCNO mutations Child Chronic diseases Ciliary motility disorders |
| topic_facet | CCNO mutations Child Chronic diseases Ciliary motility disorders |
| url | http://hdl.handle.net/10451/48683 |
| visible | 1 |