TY - JOUR
T1 - Partial recessive IFN-γR1 deficiency
T2 - Genetic, immunological and clinical features of 14 patients from 11 kindreds
AU - Sologuren, Ithaisa
AU - Boisson-Dupuis, Stéphanie
AU - Pestano, Jose
AU - Vincent, Quentin Benoit
AU - Fernández-Pérez, Leandro
AU - Chapgier, Ariane
AU - Cárdenes, María
AU - Feinberg, Jacqueline
AU - García-Laorden, M. Isabel
AU - Picard, Capucine
AU - Santiago, Esther
AU - Kong, Xiaofei
AU - Jannière, Lucile
AU - Colino, Elena
AU - Herrera-Ramos, Estefanía
AU - Francés, Adela
AU - Navarrete, Carmen
AU - Blanche, Stéphane
AU - Faria, Emilia
AU - Remiszewski, Paweł
AU - Cordeiro, Ana
AU - Freeman, Alexandra
AU - Holland, Steven
AU - Abarca, Katia
AU - Valerón-Lemaur, Mónica
AU - Gonçalo-Marques, José
AU - Silveira, Luisa
AU - García-Castellano, José Manuel
AU - Caminero, José
AU - Pérez-Arellano, José Luis
AU - Bustamante, José Luerez Arellano
AU - Abel, Laurent
AU - Casanova, Jean Laurent
AU - Rodríguez-Gallego, Carlos
N1 - Funding Information:
This work was supported by grants from the Institute of Health Carlos III, Ministry of Health (RedRespira-ISCiii-RTIC-03/ 11, FIS 06/1031, with the funding of European Regional Development Fund-European Social Fund—FEDER-FSE); Fundación Canaria de Investigación y Salud (Canarian Government, INREDCAN 05/06); Research Prize of Foundation Caja Rural de Canarias-Chil y Naranjo 2004; Canarian Institute for Cancer Research (ISCiii-RTICCC-C03/10 to M.C.); Proyecto Biorregion 2006 to M.I.G.-L.; and Universidad de Las Palmas de Gran Canaria (fellowship to E.H.-R.). J.-L.C. was an International Scholar of the Howard Hughes Medical Institute. The sponsors of the study had no role in designing the study, collecting, analyzing and interpreting the data, or writing the paper.
PY - 2011/4
Y1 - 2011/4
N2 - We report a series of 14 patients from 11 kindreds with recessive partial (RP)-interferon (IFN)-γR1 deficiency. The I87T mutation was found in nine homozygous patients from Chile, Portugal and Poland, and the V63G mutation was found in five homozygous patients from the Canary Islands. Founder effects accounted for the recurrence of both mutations. The most recent common ancestors of the patients with the I87T and V63G mutations probably lived 1600 (875-2950) and 500 (200-1275) years ago, respectively. The two alleles confer phenotypes that are similar but differ in terms of IFN-γR1 levels and residual response to IFN-γ. The patients suffered from bacillus Calmette-Guérin-osis (n = 6), environmental mycobacteriosis (n = 6) or tuberculosis (n = 1). One patient did not suffer from mycobacterial infections but had disseminated salmonellosis, which was also present in two other patients. Age at onset of the first environmental mycobacterial disease differed widely between patients, with a mean value of 11.25 ± 9.13 years. Thirteen patients survived until the age of 14.82 ± 11.2 years, and one patient died at the age of 7 years, 9 days after the diagnosis of long-term Mycobacterium avium infection and the initiation of antimycobacterial treatment. Up to 10 patients are currently free of infection with no prophylaxis. The clinical heterogeneity of the 14 patients was not clearly related to either IFNGR1 genotype or the resulting cellular phenotype. RP-IFN-γR1 deficiency is, thus, more common than initially thought and should be considered in both children and adults with mild or severe mycobacterial diseases.
AB - We report a series of 14 patients from 11 kindreds with recessive partial (RP)-interferon (IFN)-γR1 deficiency. The I87T mutation was found in nine homozygous patients from Chile, Portugal and Poland, and the V63G mutation was found in five homozygous patients from the Canary Islands. Founder effects accounted for the recurrence of both mutations. The most recent common ancestors of the patients with the I87T and V63G mutations probably lived 1600 (875-2950) and 500 (200-1275) years ago, respectively. The two alleles confer phenotypes that are similar but differ in terms of IFN-γR1 levels and residual response to IFN-γ. The patients suffered from bacillus Calmette-Guérin-osis (n = 6), environmental mycobacteriosis (n = 6) or tuberculosis (n = 1). One patient did not suffer from mycobacterial infections but had disseminated salmonellosis, which was also present in two other patients. Age at onset of the first environmental mycobacterial disease differed widely between patients, with a mean value of 11.25 ± 9.13 years. Thirteen patients survived until the age of 14.82 ± 11.2 years, and one patient died at the age of 7 years, 9 days after the diagnosis of long-term Mycobacterium avium infection and the initiation of antimycobacterial treatment. Up to 10 patients are currently free of infection with no prophylaxis. The clinical heterogeneity of the 14 patients was not clearly related to either IFNGR1 genotype or the resulting cellular phenotype. RP-IFN-γR1 deficiency is, thus, more common than initially thought and should be considered in both children and adults with mild or severe mycobacterial diseases.
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U2 - 10.1093/hmg/ddr029
DO - 10.1093/hmg/ddr029
M3 - Article
C2 - 21266457
AN - SCOPUS:79953072406
SN - 0964-6906
VL - 20
SP - 1509
EP - 1523
JO - Human molecular genetics
JF - Human molecular genetics
IS - 8
M1 - ddr029
ER -