Risk of Atypical HUS Among Family Members of Patients Carrying Complement Regulatory Gene Abnormality.
Kidney Int Rep
; 6(6): 1614-1621, 2021 Jun.
Article
em En
| MEDLINE
| ID: mdl-34169201
ABSTRACT
INTRODUCTION:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article