Partial recessive IFN-γR1 deficiency: genetic, immunological and clinical features of 14 patients from 11 kindreds.
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.
Department of Immunology, Gran Canaria Dr Negrín University Hospital, Las Palmas de Gran Canaria, Spain.
Ithaisa
I
Sologuren
Stéphanie
S
Boisson-Dupuis
Jose
J
Pestano
Quentin Benoit
QB
Vincent
Leandro
L
Fernández-Pérez
Ariane
A
Chapgier
María
M
Cárdenes
Jacqueline
J
Feinberg
M Isabel
MI
García-Laorden
Capucine
C
Picard
Esther
E
Santiago
Xiaofei
X
Kong
Lucile
L
Jannière
Elena
E
Colino
Estefanía
E
Herrera-Ramos
Adela
A
Francés
Carmen
C
Navarrete
Stéphane
S
Blanche
Emilia
E
Faria
Pawel
P
Remiszewski
Ana
A
Cordeiro
Alexandra
A
Freeman
Steven
S
Holland
Katia
K
Abarca
Mónica
M
Valerón-Lemaur
José
J
Gonçalo-Marques
Luisa
L
Silveira
José Manuel
JM
García-Castellano
José
J
Caminero
José Luis
JL
Pérez-Arellano
Jacinta
J
Bustamante
Laurent
L
Abel
Jean-Laurent
JL
Casanova
Carlos
C
Rodríguez-Gallego
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D018703:Founder Effect; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D020125:Mutation, Missense; D009164:Mycobacterium Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D009162:Mycobacterium avium; D009163:Mycobacterium bovis; D010019:Osteomyelitis / Q000235:genetics / Q000382:microbiology; D010375:Pedigree; D010641:Phenotype; D010766:Phosphorylation; D018410:Pneumonia, Bacterial / Q000235:genetics; D021381:Protein Transport; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D012475:Salmonella; D012480:Salmonella Infections / Q000235:genetics; D014376:Tuberculosis / Q000235:genetics / Q000382:microbiology / Q000401:mortality; D055815:Young Adult; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human
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