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Table 1 Genetic mutation, inheritance and disease patterns in different series

From: An unprecedented COPA gene mutation in two patients in the same family: comparative clinical analysis of newly reported patients with other known COPA gene mutations

Group Gene mutation, inheritance and family history Diseases pattern
Watkin et al., 2015 [3]
and Tsui et al., 2018 [2]
(n = 21)
c.698G > A p.Arg233His,
c.728A > G p.Asp243Gly,
c.721G > A p.Glu241Lys,
c.690G > T p.Lys230Asn.
Four missense mutations in exons 8 and 9 of the COPA gene.
Heritance: Autosomal dominant.
(c.721G > A), (c.728A > G) and (c.698G > A) mutations: Mostly incomplete penetrance but showed complete penetrance over two generations in only one family.
(c.690G > T) mutation: Inconclusive regarding penetrance (carrier is just 1 year old and is asymptomatic at this point)
20/21 (95%) had Polyarthritis, 21/21 (100%) had a progressive pulmonary disease.
4 (19%) patients had an immune-mediated renal disease.
Two families with c.721G > A p. Glu241Lys mutation did not have renal disease.
One patient had a recurrent nonspecific rash.
Brynjar O. Jensson, et al. 2017 [4]
(n = 3)
Mutation: c.721G > A p. Glu241Lys.
Heritance: Index case had de novo mutation as both of his parents were negative for gene mutation and were healthy at the time of writing.
2/3 (66%) had autosomal dominant with complete penetrance.
3/3 (100%) had polyarthritis.
3/3 (100%) had a progressive pulmonary disease.
No renal involvement.
1/3 (33%) had nail clubbing.
Brennan MA. et al. 2017 [8]
(n = 1)
c.727G > A/p. Asp243Asn. Substitution in exon-9.
Heritance: De novo mutation.
No family history but parental genetic status not available.
1/1 (100%) -had erosive destructive Poly JIA at age 30 months of age as presentation.
At age 6 years, presented with progressive restrictive lung disease
Positive for CF gene test [CFTR: genotype F508del/R117H(7 T). Sweat chlorides 52 and 38 mmol/L],
GERD (needed fundoplication) Developed Systemic Lupus Erythematosus later in the disease course.
Developed MAS. No renal disease. Positive for finger clubbing
Volpi S 2018 [7]
(n = 1)
Mutation: c.698GNA.
Heritance: Autosomal dominant with variable penetrance.
Mother of the index case was identified to be an asymptomatic carrier of same gene mutation.
Presented with progressive severe destructive polyarthritis
Years later presented with progressive restrictive pulmonary diseases. No pulmonary hemorrhage or hemoptysis.
No renal disease.
Patwardhan A et al. Mutation: c.722A > C p, Glu241Ala.
Heritance: Autosomal dominant with complete penetrance. Son-the index case and his father.
Sibling of the index case is negative for mutation.
2/2 (100%)-Presented with progressive mixed obstructive and restrictive lung disease, chronic respiratory insufficiency, cough, oxygen requirement, artificial ventilation, pulmonary hemorrhages.
1/2 (50%)- Father had arthralgias and later developed destructive polyarthritis.
0/2 (0%) -No renal disease
  1. NB: (CF Cystic Fibrosis, MAS Macrophage activation syndrome. JIA Juvenile idiopathic arthritis. ENA Extractable nuclear antibodies. DLCO Diffusing capacity of the lungs for carbon monoxide. GERD Gastroesophageal reflux disease. Tsui al. group had common patients with Levi B Watkin et al. group but had more detailed information on pulmonary symptoms