Emma M. Haapaniemi, MD, Christopher L

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Presentation transcript:

Combined immunodeficiency and hypoglycemia associated with mutations in hypoxia upregulated 1 Emma M. Haapaniemi, MD, Christopher L. Fogarty, MSc, Salla Keskitalo, MSc, Shintaro Katayama, PhD, Helena Vihinen, DSc, Mette Ilander, PhD, Satu Mustjoki, MD, Kaarel Krjutškov, PhD, Markku Lehto, PhD, Timo Hautala, MD, Ove Eriksson, PhD, Eija Jokitalo, PhD, Vidya Velagapudi, PhD, Markku Varjosalo, PhD, Mikko Seppänen, MD, Juha Kere, MD Journal of Allergy and Clinical Immunology Volume 139, Issue 4, Pages 1391-1393.e11 (April 2017) DOI: 10.1016/j.jaci.2016.09.050 Copyright © 2016 The Authors Terms and Conditions

Fig 1 A, HYOU1 structure4 with the observed mutations. B, RNA expression profile in primary fibroblasts. C, Interaction partners of WT and mutant HYOU1 proteins as determined by affinity-purification mass-spectrometry (AP-MS). Black line denotes mitochondrial proteins. D and E, Electron micrograph figures of control (left) and patient (right) neutrophils show abundant mitochondria. F, Comparison of enriched pathways between RNA sequencing, AP-MS (denoted as binding assay), and targeted metabolite profiling (referred as metabolic assay). Poly-Phen, Polymorphism Phenotyping (algorithm); SIFT, Sorting Intolerant from Tolerant (algorithm). Journal of Allergy and Clinical Immunology 2017 139, 1391-1393.e11DOI: (10.1016/j.jaci.2016.09.050) Copyright © 2016 The Authors Terms and Conditions

Fig E1 A, Sanger sequencing of the HYOU1 mutants in index patient and her parents. B, HYOU1 protein expression and subcellular localization (C) in Flp-In 293 T-REx cells. Both mutants are expressed equally, and the subcellular localization is unaltered. DAPI, 4′-6-diamidino-2-phenylindole, dihydrochloride; HA, Hemaggluting tag. Journal of Allergy and Clinical Immunology 2017 139, 1391-1393.e11DOI: (10.1016/j.jaci.2016.09.050) Copyright © 2016 The Authors Terms and Conditions

Fig E2 Some of the ectopic interaction partners of the mutant HYOU1 proteins were upregulated on the RNA sequencing of patient primary fibroblasts. Genes with statistically significant differential expression (P < .05) are shown. NME2, Nucleoside diphosphate kinase B; PTMA, prothymosin alpha; PTMS, parathymosin; TPI1, triosephosphate isomerase 1. Journal of Allergy and Clinical Immunology 2017 139, 1391-1393.e11DOI: (10.1016/j.jaci.2016.09.050) Copyright © 2016 The Authors Terms and Conditions

Fig E3 A, Significantly altered metabolites in primary fibroblasts. B, Mitochondrial respiration capacity on patient and healthy control primary fibroblasts. The patient cells perform on low normal range, but no statistically significant abnormality is evident. Time points between 0 and 20 minutes evaluate basal mitochondrial respiration, 20 to 50 minutes cellular ATP production, and 50 to 80 minutes the maximal respiratory capacity. OCR, Oxygen consumption rate. Journal of Allergy and Clinical Immunology 2017 139, 1391-1393.e11DOI: (10.1016/j.jaci.2016.09.050) Copyright © 2016 The Authors Terms and Conditions