Paternal uniparental isodisomy of chromosome 6 causing a complex syndrome including complete IFN-gamma receptor 1 deficiency.
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency associated with clinical disease caused by weakly virulent mycobacterial species. Interferon gamma receptor 1 (IFN-gammaR1) deficiency is a genetic etiology of MSMD. We describe the clinical and genetic features of a 7-year-old Italian boy suffering from MSMD associated with a complex phenotype, including neonatal hyperglycemia, neuromuscular disease, and dysmorphic features. The child also developed necrotizing pneumonia caused by Rhodococcus equi. The child is homozygous for a nonsense mutation in exon 3 of IFNGR1 as a result of paternal uniparental disomy (UPD) of the entire chromosome 6. This is the first reported case of uniparental disomy resulting in a complex phenotype including MSMD.
Prando
Carolina
C
Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA.
Boisson-Dupuis
Stéphanie
S
Grant
Audrey V
AV
Kong
Xiao-Fei
XF
Bustamante
Jacinta
J
Feinberg
Jacqueline
J
Chapgier
Ariane
A
Rose
Yoann
Y
Jannière
Lucile
L
Rizzardi
Elena
E
Zhang
Qiuping
Q
Shanahan
Catherine M
CM
Viollet
Louis
L
Lyonnet
Stanislas
S
Abel
Laurent
L
Ruga
Ezia Maria
EM
Casanova
Jean-Laurent
JL
D000015:Abnormalities, Multiple / Q000235:genetics*; D000193:Actinomycetales Infections / Q000235:genetics; D002648:Child; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005091:Exons; D005220:Fathers; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D009164:Mycobacterium Infections / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017471:Receptors, Interferon / Q000172:deficiency* / Q000235:genetics*; D016929:Rhodococcus equi; D013577:Syndrome; D024182:Uniparental Disomy / Q000235:genetics*; D000096743:Interferon gamma Receptor
D018389:Codon, Nonsense; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor