Journal article

Haploinsufficiency at the human IFNGR2 locus contributes to mycobacterial disease.

Xiao-Fei Kong, Guillaume Vogt, Yuval Itan, Anna Macura-Biegun, Anna Szaflarska, Danuta Kowalczyk, Ariane Chapgier, Avinash Abhyankar, Dieter Furthner, Claudia Djambas Khayat, Satoshi Okada, Vanessa L Bryant, Dusan Bogunovic, Alexandra Kreins, Marcela Moncada-Vélez, Mélanie Migaud, Sulaiman Al-Ajaji, Saleh Al-Muhsen, Steven M Holland, Laurent Abel Show all

Hum Mol Genet | Published : 2013


Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare syndrome, the known genetic etiologies of which impair the production of, or the response to interferon-gamma (IFN-γ). We report here a patient (P1) with MSMD whose cells display mildly impaired responses to IFN-γ, at levels, however, similar to those from MSMD patients with autosomal recessive (AR) partial IFN-γR2 or STAT1 deficiency. Whole-exome sequencing (WES) and Sanger sequencing revealed only one candidate variation for both MSMD-causing and IFN-γ-related genes. P1 carried a heterozygous frame-shift IFNGR2 mutation inherited from her father. We show that the mutant allele is intrinsically loss-of-function and not domi..

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University of Melbourne Researchers