Paternal uniparental isodisomy of chromosome 6 causing a complex syndrome including complete IFN-gamma receptor 1 deficiency

Am J Med Genet A. 2010 Mar;152A(3):622-9. doi: 10.1002/ajmg.a.33291.

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Actinomycetales Infections / genetics
  • Child
  • Chromosomes, Human, Pair 6 / genetics*
  • Codon, Nonsense
  • DNA Mutational Analysis
  • Exons
  • Fathers
  • Female
  • Homozygote
  • Humans
  • Interferon gamma Receptor
  • Male
  • Mycobacterium Infections / genetics*
  • Pedigree
  • Phenotype
  • Receptors, Interferon / deficiency*
  • Receptors, Interferon / genetics*
  • Rhodococcus equi
  • Syndrome
  • Uniparental Disomy / genetics*

Substances

  • Codon, Nonsense
  • Receptors, Interferon