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Prevalence and phenotype associations of complement factor I mutations in geographic atrophy

Lookup NU author(s): Professor David SteelORCiD, Professor David KavanaghORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Rare variants in the complement factor I (CFI) gene, associated with low serum factor I (FI) levels, are strong risk factors for developing the advanced stages of age-related macular degeneration (AMD). No studies have been undertaken on the prevalence of disease-causing CFI mutations in patients with geographic atrophy (GA) secondary to AMD. A multicenter, cross-sectional, noninterventional study was undertaken to identify the prevalence of pathogenic rare CFI gene variants in an unselected cohort of patients with GA and low FI levels. A genotype-phenotype study was performed. Four hundred and sixty-eight patients with GA secondary to AMD were recruited to the study, and 19.4% (n = 91) demonstrated a low serum FI concentration (below 15.6 μg/ml). CFI gene sequencing on these patients resulted in the detection of rare CFI variants in 4.7% (n = 22) of recruited patients. The prevalence of CFI variants in patients with low serum FI levels and GA was 25%. Of the total patients recruited, 3.2% (n = 15) expressed a CFI variant classified as pathogenic or likely pathogenic. The presence of reticular pseudodrusen was detected in all patients with pathogenic CFI gene variants. Patients with pathogenic CFI gene variants and low serum FI levels might be suitable for FI supplementation in therapeutic trials.

Publication metadata

Author(s): Khan AH, Sutton J, Cree AJ, Khandhadia S, DeSalvo G, Tobin J, Prakash P, Arora R, Amoaku W, CharbelIssa P, MacLaren RE, Bishop PN, Peto T, Mohamed Q, Steel DH, Sivaprasad S, Bailey C, Menon G, Kavanagh D, Lotery AJ

Publication type: Article

Publication status: Published

Journal: Human Mutation

Year: 2021

Volume: 42

Issue: 9

Pages: 1139-1152

Print publication date: 01/09/2021

Online publication date: 21/06/2021

Acceptance date: 13/06/2021

Date deposited: 02/07/2021

ISSN (print): 1059-7794

ISSN (electronic): 1098-1004

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/humu.24242

PubMed id: 34153144


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Funder referenceFunder name
Gyroscope Therapeutics Limited