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Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features

BACKGROUND: Copa syndrome is a rare autosomal dominant disorder with abnormal intracellular vesicle trafficking. The objective of this work is to expand the knowledge about this disorder by delineating phenotypic features of an unreported COPA family. METHODS AND RESULTS: A heterozygous missense var...

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Autores principales: Taveira-DaSilva, Angelo M, Markello, Thomas C, Kleiner, David E, Jones, Amanda M, Groden, Catherine, Macnamara, Ellen, Yokoyama, Tadafumi, Gahl, William A, Gochuico, Bernadette R, Moss, Joel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6860403/
https://www.ncbi.nlm.nih.gov/pubmed/30385646
http://dx.doi.org/10.1136/jmedgenet-2018-105560
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author Taveira-DaSilva, Angelo M
Markello, Thomas C
Kleiner, David E
Jones, Amanda M
Groden, Catherine
Macnamara, Ellen
Yokoyama, Tadafumi
Gahl, William A
Gochuico, Bernadette R
Moss, Joel
author_facet Taveira-DaSilva, Angelo M
Markello, Thomas C
Kleiner, David E
Jones, Amanda M
Groden, Catherine
Macnamara, Ellen
Yokoyama, Tadafumi
Gahl, William A
Gochuico, Bernadette R
Moss, Joel
author_sort Taveira-DaSilva, Angelo M
collection PubMed
description BACKGROUND: Copa syndrome is a rare autosomal dominant disorder with abnormal intracellular vesicle trafficking. The objective of this work is to expand the knowledge about this disorder by delineating phenotypic features of an unreported COPA family. METHODS AND RESULTS: A heterozygous missense variant (c.698 G>A, p.Arg233His) in COPA was identified in four members of a three-generation kindred with lung, autoimmune and malignant disease of unknown aetiology. Ages of onset were 56, 26, 16 and 1 year, with earlier age of onset in successive generations. Presenting symptoms were cough and dyspnoea. Findings included small lung cysts, follicular bronchiolitis, interstitial lung disease, neuroendocrine cell hyperplasia, rheumatoid arthritis, avascular necrosis and select abnormal autoimmune serologies. Neither alveolar haemorrhage nor glomerular disease were present. Features not previously associated with Copa syndrome included neuromyelitis optica, pulmonary carcinoid tumour, clear cell renal carcinoma, renal cysts, hepatic cysts, nephrolithiasis, pyelonephritis and meningitis. Longitudinal evaluations demonstrated slow progression of lung disease and extrapulmonary cysts. CONCLUSIONS: Worsening severity with successive generations may be observed in Copa syndrome. Extrapulmonary cysts, malignancies, autoimmune neurological disorders and infections are clinical features that may be associated with Copa syndrome. Further studies are indicated to fully define the phenotypic spectrum of this disorder.
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spelling pubmed-68604032019-12-03 Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features Taveira-DaSilva, Angelo M Markello, Thomas C Kleiner, David E Jones, Amanda M Groden, Catherine Macnamara, Ellen Yokoyama, Tadafumi Gahl, William A Gochuico, Bernadette R Moss, Joel J Med Genet Phenotypes BACKGROUND: Copa syndrome is a rare autosomal dominant disorder with abnormal intracellular vesicle trafficking. The objective of this work is to expand the knowledge about this disorder by delineating phenotypic features of an unreported COPA family. METHODS AND RESULTS: A heterozygous missense variant (c.698 G>A, p.Arg233His) in COPA was identified in four members of a three-generation kindred with lung, autoimmune and malignant disease of unknown aetiology. Ages of onset were 56, 26, 16 and 1 year, with earlier age of onset in successive generations. Presenting symptoms were cough and dyspnoea. Findings included small lung cysts, follicular bronchiolitis, interstitial lung disease, neuroendocrine cell hyperplasia, rheumatoid arthritis, avascular necrosis and select abnormal autoimmune serologies. Neither alveolar haemorrhage nor glomerular disease were present. Features not previously associated with Copa syndrome included neuromyelitis optica, pulmonary carcinoid tumour, clear cell renal carcinoma, renal cysts, hepatic cysts, nephrolithiasis, pyelonephritis and meningitis. Longitudinal evaluations demonstrated slow progression of lung disease and extrapulmonary cysts. CONCLUSIONS: Worsening severity with successive generations may be observed in Copa syndrome. Extrapulmonary cysts, malignancies, autoimmune neurological disorders and infections are clinical features that may be associated with Copa syndrome. Further studies are indicated to fully define the phenotypic spectrum of this disorder. BMJ Publishing Group 2019-11 2018-11-01 /pmc/articles/PMC6860403/ /pubmed/30385646 http://dx.doi.org/10.1136/jmedgenet-2018-105560 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Phenotypes
Taveira-DaSilva, Angelo M
Markello, Thomas C
Kleiner, David E
Jones, Amanda M
Groden, Catherine
Macnamara, Ellen
Yokoyama, Tadafumi
Gahl, William A
Gochuico, Bernadette R
Moss, Joel
Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features
title Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features
title_full Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features
title_fullStr Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features
title_full_unstemmed Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features
title_short Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features
title_sort expanding the phenotype of copa syndrome: a kindred with typical and atypical features
topic Phenotypes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6860403/
https://www.ncbi.nlm.nih.gov/pubmed/30385646
http://dx.doi.org/10.1136/jmedgenet-2018-105560
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