Risk of Atypical HUS Among Family Members of Patients Carrying Complement Regulatory Gene Abnormality.
aHUS
complement genes
penetrance
Journal
Kidney international reports
ISSN: 2468-0249
Titre abrégé: Kidney Int Rep
Pays: United States
ID NLM: 101684752
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
03
02
2021
revised:
08
03
2021
accepted:
15
03
2021
entrez:
25
6
2021
pubmed:
26
6
2021
medline:
26
6
2021
Statut:
epublish
Résumé
Atypical hemolytic uremic syndrome (aHUS) is mainly due to complement regulatory gene abnormalities with a dominant pattern but incomplete penetrance. Thus, healthy carriers can be identified in any family of aHUS patients, but it is unpredictable if they will eventually develop aHUS. Patients are screened for 10 complement regulatory gene abnormalities and once a genetic alteration is identified, the search is extended to at-risk family members. The present cohort study includes 257 subjects from 71 families: 99 aHUS patients (71 index cases + 28 affected family members) and 158 healthy relatives with a documented complement gene abnormality. Fourteen families (19.7%) experienced multiple cases. Over a cumulative observation period of 7595 person-years, only 28 family members carrying gene mutations experienced aHUS (overall penetrance of 20%), leading to a disease rate of 3.69 events for 1000 person-years. The disease rate was 7.47 per 1000 person-years among siblings, 6.29 among offspring, 2.01 among parents, 1.84 among carriers of variants of uncertain significance, and 4.43 among carriers of causative variants. The penetrance of aHUS seems a lot lower than previously reported. Moreover, the disease risk is higher in carriers of causative variants and is not equally distributed among generations: siblings and the offspring of patients have a much greater disease risk than parents. However, risk calculation may depend on variant classification that could change over time.
Identifiants
pubmed: 34169201
doi: 10.1016/j.ekir.2021.03.885
pii: S2468-0249(21)01033-0
pmc: PMC8207326
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1614-1621Informations de copyright
© 2021 International Society of Nephrology. Published by Elsevier Inc.
Références
Pediatr Nephrol. 2013 Nov;28(11):2221-5
pubmed: 23880784
Kidney Int. 2017 Mar;91(3):539-551
pubmed: 27989322
Lancet. 2017 Aug 12;390(10095):681-696
pubmed: 28242109
J Am Soc Nephrol. 2014 Jan;25(1):55-64
pubmed: 24029428
Am J Kidney Dis. 2015 Feb;65(2):342
pubmed: 25616634
Kidney Int. 2016 Mar;89(3):701-11
pubmed: 26880462
Am J Kidney Dis. 2015 Jul;66(1):172-3
pubmed: 26111906
Ann Hum Genet. 2010 Jan;74(1):17-26
pubmed: 20059470
Semin Thromb Hemost. 2014 Jun;40(4):422-30
pubmed: 24799305
N Engl J Med. 2009 Jul 23;361(4):345-57
pubmed: 19625716
J Thromb Haemost. 2014 Sep;12(9):1440-8
pubmed: 24853860
Blood. 2014 Sep 11;124(11):1715-26
pubmed: 25037630
Blood. 2007 Sep 1;110(5):1516-8
pubmed: 17495132
Clin J Am Soc Nephrol. 2013 Apr;8(4):554-62
pubmed: 23307876
Am J Kidney Dis. 2014 Jan;63(1):40-8
pubmed: 24021908
Clin Dev Immunol. 2012;2012:370426
pubmed: 23251215
Nat Genet. 2013 May;45(5):531-6
pubmed: 23542698
Clin J Am Soc Nephrol. 2017 Jan 6;12(1):50-59
pubmed: 27799617
Blood. 2010 Jan 14;115(2):158-60
pubmed: 20075170
Clin J Am Soc Nephrol. 2010 Oct;5(10):1844-59
pubmed: 20595690
Blood. 2009 Nov 5;114(19):4261-71
pubmed: 19745068
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Semin Nephrol. 2013 Nov;33(6):479-92
pubmed: 24161035
Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):240-5
pubmed: 17182750
QJM. 2016 Jan;109(1):27-33
pubmed: 25899302
Am J Kidney Dis. 2014 Oct;64(4):633-7
pubmed: 24656451
Ann N Y Acad Sci. 2005 Nov;1056:144-52
pubmed: 16387683
Am J Hum Genet. 2002 Dec;71(6):1285-95
pubmed: 12424708
Arch Dis Child. 2016 Apr;101(4):387-91
pubmed: 26729748
Blood. 2008 Dec 15;112(13):4948-52
pubmed: 18796626
Am J Kidney Dis. 2016 Jul;68(1):84-93
pubmed: 27012908
Pediatr Nephrol. 2016 Jan;31(1):15-39
pubmed: 25859752
J Immunol. 2018 Apr 1;200(7):2464-2478
pubmed: 29500241