title: Paternal uniparental isodisomy of chromosome 6 causing a complex syndrome including complete IFN-gamma receptor 1 deficiency.
abstract: 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.
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Prando
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.forename: Audrey V
authors.initials: AV
authors.lastname: Grant
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Kong
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Feinberg
authors.forename: Ariane
authors.initials: A
authors.lastname: Chapgier
authors.forename: Yoann
authors.initials: Y
authors.lastname: Rose
authors.forename: Lucile
authors.initials: L
authors.lastname: Jannière
authors.forename: Elena
authors.initials: E
authors.lastname: Rizzardi
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Zhang
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Shanahan
authors.forename: Louis
authors.initials: L
authors.lastname: Viollet
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Ezia Maria
authors.initials: EM
authors.lastname: Ruga
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: 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
chemical_list: D018389:Codon, Nonsense; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor