Liwak-Muir Urszula, Mamady Hapsatou, Naas Turaya, Wylie Quinlan, McBride Skye, Lines Matthew, Michaud Jean, Baird Stephen D, Chakraborty Pranesh K, Holcik Martin
Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
Orphanet J Rare Dis. 2016 Jun 18;11(1):79. doi: 10.1186/s13023-016-0466-3.
SIFD (Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay) is a novel form of congenital sideroblastic anemia associated with B-cell immunodeficiency, periodic fevers, and developmental delay caused by mutations in the CCA-adding enzyme TRNT1, but the precise molecular pathophysiology is not known.
We show that the disease causing mutations in patient-derived fibroblasts do not affect subcellular localization of TRNT1 and show no gross morphological differences when compared to control cells. Analysis of cellular respiration and oxidative phosphorylation (OXPHOS) complexes demonstrates that both basal and maximal respiration rates are decreased in patient cells, which may be attributed to an observed decrease in the abundance of select proteins of the OXPHOS complexes.
Our data provides further insight into cellular pathophysiology of SIFD.
伴B细胞免疫缺陷、周期性发热和发育迟缓的铁粒幼细胞贫血（SIFD）是一种新型先天性铁粒幼细胞贫血，与B细胞免疫缺陷、周期性发热以及由CCA添加酶TRNT1突变导致的发育迟缓相关，但确切的分子病理生理学尚不清楚。
我们发现，患者来源的成纤维细胞中导致疾病的突变并不影响TRNT1的亚细胞定位，与对照细胞相比也未显示出明显的形态学差异。对细胞呼吸和氧化磷酸化（OXPHOS）复合物的分析表明，患者细胞的基础呼吸率和最大呼吸率均降低，这可能归因于观察到的OXPHOS复合物中某些蛋白质丰度的下降。
我们的数据为SIFD的细胞病理生理学提供了进一步的见解。
