PT  - JOURNAL ARTICLE
AU  - Angelo M Taveira-DaSilva
AU  - Thomas C Markello
AU  - David E Kleiner
AU  - Amanda M Jones
AU  - Catherine Groden
AU  - Ellen Macnamara
AU  - Tadafumi Yokoyama
AU  - William A Gahl
AU  - Bernadette R Gochuico
AU  - Joel Moss
TI  - Expanding the phenotype of COPA syndrome: a kindred with typical and atypical features
AID  - 10.1136/jmedgenet-2018-105560
DP  - 2018 Nov 01
TA  - Journal of Medical Genetics
PG  - jmedgenet-2018-105560
4099  - http://jmg.bmj.com/content/early/2018/11/01/jmedgenet-2018-105560.short
4100  - http://jmg.bmj.com/content/early/2018/11/01/jmedgenet-2018-105560.full
AB  - 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.