F8/F9 variants in the population-based PedNet Registry cohort compared with locus-specific genetic databases of the European Association for Haemophilia and Allied Disorders and the Centers for Disease Control and Prevention Hemophilia A or Hemophilia B Mutation Project.
Labarque, Veerle ; Mancuso, Maria Elisa ; Kartal-Kaess, Mutlu ; Ljung, Rolf LU
; Mikkelsen, Torben S
and Andersson, Nadine G
LU
(2023)
In Research and practice in thrombosis and haemostasis
7(1).
- Abstract
BACKGROUND: Hemophilia A and B are caused by variants in the factor (F) VIII or FIX gene. Selective reporting may influence the distribution of variants reported in genetic databases.
OBJECTIVES: To compare the spectrum of
F8 and
F9 variants in an international population-based pediatric cohort (PedNet Registry) with the spectrum found in the European Association for Haemophilia and Allied Disorders (EAHAD) and the Centers for Disease Control and Prevention Hemophilia A or Hemophilia B Mutation Project (CHAMP/CHBMP) databases.
METHODS: All patients registered in the PedNet Registry on January 1, 2021 were included in this study. As comparators, data from patients with severe hemophilia included in the... (More)
BACKGROUND: Hemophilia A and B are caused by variants in the factor (F) VIII or FIX gene. Selective reporting may influence the distribution of variants reported in genetic databases.
OBJECTIVES: To compare the spectrum of
F8 and
F9 variants in an international population-based pediatric cohort (PedNet Registry) with the spectrum found in the European Association for Haemophilia and Allied Disorders (EAHAD) and the Centers for Disease Control and Prevention Hemophilia A or Hemophilia B Mutation Project (CHAMP/CHBMP) databases.
METHODS: All patients registered in the PedNet Registry on January 1, 2021 were included in this study. As comparators, data from patients with severe hemophilia included in the CHAMP/CHBMP registry (US center data) and EAHAD were used.
RESULTS: Genetic information was available for 1941 patients. Intron 22 inversion was present in 52% of patients with severe hemophilia A; frameshift (36%), missense (28%), and nonsense (20%) were the most frequent variants in patients with severe hemophilia A who were inversion-negative. The most frequent variants in severe hemophilia B were missense (48%). In nonsevere disease, most variants were missense variants (moderate hemophilia A: 91%; mild hemophilia A: 95%, moderate and mild hemophilia B: 86% each). Comparison with the databases demonstrated a higher proportion of missense variants associated with severe hemophilia B in EAHAD (68%) than in PedNet (48%) and CHBMP (46%).
CONCLUSION: The PedNet population-based cohort provides an alternative to the established databases, which collect data by selective reporting, as it is a well-maintained database covering the full spectrum of pathogenic
(Less)
F8 and
F9 variants, and indicates the number of patients affected by each particular variant.
- author
- Labarque, Veerle
; Mancuso, Maria Elisa
; Kartal-Kaess, Mutlu
; Ljung, Rolf
LU
; Mikkelsen, Torben S
and Andersson, Nadine G
LU
- organization
- publishing date
- 2023-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Research and practice in thrombosis and haemostasis
- volume
- 7
- issue
- 1
- article number
- 100036
- pages
- 9 pages
- publisher
- Wiley
- external identifiers
-
- scopus:85153708254
- pmid:36798899
- ISSN
- 2475-0379
- DOI
- 10.1016/j.rpth.2023.100036
- language
- English
- LU publication?
- yes
- additional info
- © 2023 The Authors.
- id
- 379bbdda-6e55-42aa-ba02-acc181a55733
- date added to LUP
- 2023-02-20 13:07:10
- date last changed
- 2024-04-19 20:16:44
@article{379bbdda-6e55-42aa-ba02-acc181a55733,
abstract = {{<p>BACKGROUND: Hemophilia A and B are caused by variants in the factor (F) VIII or FIX gene. Selective reporting may influence the distribution of variants reported in genetic databases.</p><p>OBJECTIVES: To compare the spectrum of <br>
F8 and <br>
F9 variants in an international population-based pediatric cohort (PedNet Registry) with the spectrum found in the European Association for Haemophilia and Allied Disorders (EAHAD) and the Centers for Disease Control and Prevention Hemophilia A or Hemophilia B Mutation Project (CHAMP/CHBMP) databases.<br>
</p><p>METHODS: All patients registered in the PedNet Registry on January 1, 2021 were included in this study. As comparators, data from patients with severe hemophilia included in the CHAMP/CHBMP registry (US center data) and EAHAD were used.</p><p>RESULTS: Genetic information was available for 1941 patients. Intron 22 inversion was present in 52% of patients with severe hemophilia A; frameshift (36%), missense (28%), and nonsense (20%) were the most frequent variants in patients with severe hemophilia A who were inversion-negative. The most frequent variants in severe hemophilia B were missense (48%). In nonsevere disease, most variants were missense variants (moderate hemophilia A: 91%; mild hemophilia A: 95%, moderate and mild hemophilia B: 86% each). Comparison with the databases demonstrated a higher proportion of missense variants associated with severe hemophilia B in EAHAD (68%) than in PedNet (48%) and CHBMP (46%).</p><p>CONCLUSION: The PedNet population-based cohort provides an alternative to the established databases, which collect data by selective reporting, as it is a well-maintained database covering the full spectrum of pathogenic <br>
F8 and <br>
F9 variants, and indicates the number of patients affected by each particular variant.<br>
</p>}},
author = {{Labarque, Veerle and Mancuso, Maria Elisa and Kartal-Kaess, Mutlu and Ljung, Rolf and Mikkelsen, Torben S and Andersson, Nadine G}},
issn = {{2475-0379}},
language = {{eng}},
number = {{1}},
publisher = {{Wiley}},
series = {{Research and practice in thrombosis and haemostasis}},
title = {{F8/F9 variants in the population-based PedNet Registry cohort compared with locus-specific genetic databases of the European Association for Haemophilia and Allied Disorders and the Centers for Disease Control and Prevention Hemophilia A or Hemophilia B Mutation Project.}},
url = {{http://dx.doi.org/10.1016/j.rpth.2023.100036}},
doi = {{10.1016/j.rpth.2023.100036}},
volume = {{7}},
year = {{2023}},
}