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

Prevalence and phenotype associations of complement factor I mutations in geographic atrophy
Prevalence and phenotype associations of complement factor I mutations in geographic atrophy
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 multi-centre, cross-sectional, non-interventional 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 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 total patients recruited, 3.2% (n=15) expressed a CFI variant classified as pathogenic or likely pathogenic. The presence of reticular pseudodrusen (RPD) 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.
age-related macular degeneration, complement factor I, factor I, geographic atrophy, reticular pseudodrusen
1059-7794
1139-1152
Khan, Adnan
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Sutton, Janice
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Cree, Angela
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Khandhadia, Samir
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De Salvo, Gabriella
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Tobin, John
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Prakash, Priya
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Arora, Rashi
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Amoaku, Winfried
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Charbel Issa, Peter
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MacLaren, Robert E.
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Bishop, Paul N.
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Peto, Tunde
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Mohamed, Quresh
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Steel, David H.
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Sivaprasad, Sobha
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Bailey, Clare
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Menon, Geeta
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Kavanagh, David
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Lotery, Andrew
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Khan, Adnan
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Sutton, Janice
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Cree, Angela
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Khandhadia, Samir
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De Salvo, Gabriella
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Tobin, John
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Prakash, Priya
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Arora, Rashi
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Amoaku, Winfried
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Charbel Issa, Peter
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MacLaren, Robert E.
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Bishop, Paul N.
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Peto, Tunde
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Mohamed, Quresh
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Steel, David H.
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Sivaprasad, Sobha
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Bailey, Clare
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Menon, Geeta
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Kavanagh, David
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Lotery, Andrew
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Khan, Adnan, Sutton, Janice, Cree, Angela, Khandhadia, Samir, De Salvo, Gabriella, Tobin, John, Prakash, Priya, Arora, Rashi, Amoaku, Winfried, Charbel Issa, Peter, MacLaren, Robert E., Bishop, Paul N., Peto, Tunde, Mohamed, Quresh, Steel, David H., Sivaprasad, Sobha, Bailey, Clare, Menon, Geeta, Kavanagh, David and Lotery, Andrew (2021) Prevalence and phenotype associations of complement factor I mutations in geographic atrophy. Human Mutation, 42 (9), 1139-1152. (doi:10.1002/humu.24242).

Record type: Article

Abstract

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 multi-centre, cross-sectional, non-interventional 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 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 total patients recruited, 3.2% (n=15) expressed a CFI variant classified as pathogenic or likely pathogenic. The presence of reticular pseudodrusen (RPD) 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.

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CFI MANUSCRIPT ACCEPTED - Accepted Manuscript
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More information

Accepted/In Press date: 13 June 2021
e-pub ahead of print date: 21 June 2021
Published date: September 2021
Keywords: age-related macular degeneration, complement factor I, factor I, geographic atrophy, reticular pseudodrusen

Identifiers

Local EPrints ID: 449882
URI: http://eprints.soton.ac.uk/id/eprint/449882
ISSN: 1059-7794
PURE UUID: 13730cc0-feb0-4566-ac62-3bffac158f39
ORCID for Adnan Khan: ORCID iD orcid.org/0000-0001-8153-8002
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305

Catalogue record

Date deposited: 23 Jun 2021 16:31
Last modified: 12 Nov 2021 03:08

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Contributors

Author: Adnan Khan ORCID iD
Author: Janice Sutton
Author: Angela Cree
Author: Samir Khandhadia
Author: Gabriella De Salvo
Author: John Tobin
Author: Priya Prakash
Author: Rashi Arora
Author: Winfried Amoaku
Author: Peter Charbel Issa
Author: Robert E. MacLaren
Author: Paul N. Bishop
Author: Tunde Peto
Author: Quresh Mohamed
Author: David H. Steel
Author: Sobha Sivaprasad
Author: Clare Bailey
Author: Geeta Menon
Author: David Kavanagh
Author: Andrew Lotery ORCID iD

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